bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients
Authors: Wong Carlos King Ho , Lui David Tak Wai , Xiong Xi , Chui Celine Sze Ling , Lai Francisco Tsz Tsun , Li Xue , Wan Eric Yuk Fai , Cheung Ching Lung , Lee Chi Ho , Woo Yu Cho , Au Ivan Chi Ho , Chung Matthew Shing Hin , Cheng Franco Wing Tak , Tan Kathryn Choon Beng , Wong Ian Chi Kei 
Published: October 2022

Abstract
Background
In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset.

Methods
We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves’ disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression.

Results
A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670–1.114; CoronaVac: IRR 0.707, 95% CI 0.549–0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716–1.159; CoronaVac: IRR 0.778, 95% CI 0.618–0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744–1.023; CoronaVac: IRR 0.830, 95% CI 0.713–0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838–1.199; CoronaVac: IRR 0.963, 95% CI 0.807–1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770–1.227; CoronaVac: IRR 0.879, 95%CI 0.693–1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833–1.246; CoronaVac: IRR 0.768, 95% CI 0.613–0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899–1.201; CoronaVac: IRR 0.911, 95% CI 0.786–1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794–1.102; CoronaVac: IRR 0.945, 95% CI 0.799–1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines.

Conclusions
Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.
Non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD in type 2 diabetic patients
Authors: Zhang Ziyin , Zhang Lu , Jiang Wangyan , Du Tingting , Yuan Gang 
Published: October 2022

Abstract
Background
Non-obese non-alcoholic fatty liver disease (NAFLD) has been reported to share clinical outcomes with its obese counterpart in the general population. However, conflicting results have been observed regarding the cardio-metabolic risk profile of non-obese NAFLD as compared to obese NAFLD. Moreover, in the context of type 2 diabetes mellitus (T2DM), this issue has been even less addressed. We hence aimed to examine the association of NAFLD with the cardio-metabolic risk profile in patients with T2DM according to their obesity status.

Methods
A total of 2,708 patients with T2DM who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed.

Results
The prevalence of NAFLD was 49.3%. NAFLD was found in 34.1% of non-obese patients and 66.0% of obese patients. Non-obese NAFLD patients had more and worse metabolic disorders than obese patients without NAFLD in both men and women. Comparable cardio-metabolic risk profiles were noted between non-obese and obese NAFLD subjects. The associations of worse cardio-metabolic risk profiles with NAFLD were overall stronger in non-obese than in obese subjects among women with T2DM, while more pronounced in obese than in non-obese subjects among men with T2DM.

Conclusion
In patients with T2DM, non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD. The associations of metabolic disorders with NAFLD were stronger in non-obese than in obese patients in women patients with T2DM.
Identification of a flavonoid C-glycosyltransferase from fern species Stenoloma chusanum and the application in synthesizing flavonoid C-glycosides in Escherichia coli
Authors: Ni Rong , Liu Xin-Yan , Zhang Jiao-Zhen , Fu Jie , Tan Hui , Zhu Ting-Ting , Zhang Jing , Wang Hai-Long , Lou Hong-Xiang , Cheng Ai-Xia 
Published: October 2022

Abstract
Background
Flavonoid C-glycosides have many beneficial effects and are widely used in food and medicine. However, plants contain a limited number of flavonoid C-glycosides, and it is challenging to create these substances chemically.

Results
To screen more robust C-glycosyltransferases (CGTs) for the biosynthesis of flavonoid C-glycosides, one CGT enzyme from Stenoloma chusanum (ScCGT1) was characterized. Biochemical analyses revealed that ScCGT1 showed the C-glycosylation activity for phloretin, 2-hydroxynaringenin, and 2-hydroxyeriodictyol. Structure modeling and mutagenesis experiments indicated that the glycosylation of ScCGT1 may be initiated by the synergistic action of conserved residue His26 and Asp14. The P164T mutation increased C-glycosylation activity by forming a hydrogen bond with the sugar donor. Furthermore, when using phloretin as a substrate, the extracellular nothofagin production obtained from the Escherichia coli strain ScCGT1-P164T reached 38 mg/L, which was 2.3-fold higher than that of the wild-type strain. Finally, it is proved that the coupling catalysis of CjFNS I/F2H and ScCGT1-P164T could convert naringenin into vitexin and isovitexin.

Conclusion
This is the first time that C-glycosyltransferase has been characterized from fern species and provides a candidate gene and strategy for the efficient production of bioactive C-glycosides using enzyme catalysis and metabolic engineering.
Attitude changes following short-form opioid overdose video education: a pilot study
Authors: Galiher Mika V. , Huffman Miranda 
Published: October 2022

Abstract
Background
Opioid overdose response training (OORT) and the need for its rapid expansion have become more significant as the opioid epidemic continues to be a health crisis in the USA. Limitation of funding and stigmatization often hinders expansion of OORT programs. Primarily due to the COVID-19 pandemic, there has been widespread transition from in-person to virtual communication. However, OORT programs may benefit from long-term use of this modality of education if it can be as effective.

Objective
To measure the change in participant attitude after a brief, virtual OORT.

Methods
A 6.5-min OORT video explained recognition of opioid overdose, appropriate response and proper administration of intranasal naloxone. Pre- and post-video scores from a 19-item survey were used to determine the video's impact on participants’ self-perceived competence and readiness to administer naloxone to a person with a suspected opioid overdose. Paired t tests were used in the analysis of pre- and post-video scores. Mann–Whitney U and Kruskal–Wallis H testing were used to compare variance between several demographic subgroups of interest.

Results
A sample of 219 participants had a significant mean difference of 15.12 (SD 9.48; 95% CI 13.86–16.39, p < 0.001) between pre- and posttest scores. Improvements were found to be greatest in content-naïve participants with lower levels of education and non-health care-related jobs than participants endorsing previous content awareness, formal naloxone training, masters, doctorate or professional degrees and health care-related jobs.

Conclusion
This pilot study demonstrated encouraging evidence that a brief, virtual, pre-recorded educational intervention improved participant-rated competence and readiness to administer intranasal naloxone in a suspected opioid overdose. Due to scalability and ability to overcome common healthcare accessibility barriers, short-form videos focused on key facts about naloxone and the benefits of its use could be part of a strategy for rapid expansion of OORT programs to mitigate opioid overdose fatalities.
Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress
Authors: Gao Junling , Lei Tong , Wang Hongyun , Luo Kai , Wang Yuanli , Cui Bingqing , Yu Zhuoran , Hu Xiaoqi , Zhang Fang , Chen Yingjie , Ding Wenjun , Lu Zhongbing 
Published: October 2022

Abstract
Background
Airborne fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) pollution is associated with the prevalence of respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease. In patients with those diseases, circulating asymmetric dimethylarginine (ADMA) levels are increased, which contributes to airway nitric oxide deficiency, oxidative stress and inflammation. Overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme degrading ADMA, exerts protective effects in animal models. However, the impact of DDAH1/ADMA on PM2.5-induced lung injury has not been investigated.

Methods
Ddah1−/− and DDAH1-transgenic mice, as well as their respective wild-type (WT) littermates, were exposed to either filtered air or airborne PM2.5 (mean daily concentration ~ 50 µg/m3) for 6 months through a whole-body exposure system. Mice were also acutely exposed to 10 mg/kg PM2.5 and/or exogenous ADMA (2 mg/kg) via intratracheal instillation every other day for 2 weeks. Inflammatory response, oxidative stress and related gene expressions in the lungs were examined. In addition, RAW264.7 cells were exposed to PM2.5 and/or ADMA and the changes in intracellular oxidative stress and inflammatory response were determined.

Results
Ddah1−/− mice developed more severe lung injury than WT mice after long-term PM2.5 exposure, which was associated with greater induction of pulmonary oxidative stress and inflammation. In the lungs of PM2.5-exposed mice, Ddah1 deficiency increased protein expression of p-p65, iNOS and Bax, and decreased protein expression of Bcl-2, SOD1 and peroxiredoxin 4. Conversely, DDAH1 overexpression significantly alleviated lung injury, attenuated pulmonary oxidative stress and inflammation, and exerted opposite effects on those proteins in PM2.5-exposed mice. In addition, exogenous ADMA administration could mimic the effect of Ddah1 deficiency on PM2.5-induced lung injury, oxidative stress and inflammation. In PM2.5-exposed macrophages, ADMA aggravated the inflammatory response and oxidative stress in an iNOS-dependent manner.

Conclusion
Our data revealed that DDAH1 has a marked protective effect on long-term PM2.5 exposure-induced lung injury.
HINT1 neuropathy in Lithuania: clinical, genetic, and functional profiling
Authors: Malcorps Matilde , Amor-Barris Silvia , Burnyte Birute , Vilimiene Ramune , Armirola-Ricaurte Camila , Grigalioniene Kristina , Ekshteyn Alexandra , Morkuniene Ausra , Vaitkevicius Arunas , De Vriendt Els , Baets Jonathan , Scherer Steven S. , Ambrozaityte Laima , Utkus Algirdas , Jordanova Albena , Peeters Kristien 
Published: October 2022

Abstract
Background
Recessive loss-of-function variations in HINT1 cause a peculiar subtype of Charcot-Marie-Tooth disease: neuromyotonia and axonal neuropathy (NMAN; OMIM[#137200]). With 25 causal variants identified worldwide, HINT1 mutations are among the most common causes of recessive neuropathy. The majority of patients are compound heterozygous or homozygous for a Slavic founder variant (c.110G>C, p.Arg37Pro) that has spread throughout Eurasia and America.

Results
In a cohort of 46 genetically unresolved Lithuanian patients with suspected inherited neuropathy, we identified eight families with HINT1 biallelic variations. Most patients displayed sensorimotor or motor-predominant axonal polyneuropathy and were homozygous for the p.Arg37Pro variant. However, in three families we identified a novel variant (c.299A>G, p.Glu100Gly). The same variant was also found in an American patient with distal hereditary motor neuropathy in compound heterozygous state (p.Arg37Pro/p.Glu100Gly). Haplotype analysis demonstrated a shared chromosomal region of 1.9 Mb between all p.Glu100Gly carriers, suggesting a founder effect. Functional characterization showed that the p.Glu100Gly variant renders a catalytically active enzyme, yet highly unstable in patient cells, thus supporting a loss-of-function mechanism.

Conclusion
Our findings broaden NMAN’s genetic epidemiology and have implications for the molecular diagnostics of inherited neuropathies in the Baltic region and beyond. Moreover, we provide mechanistic insights allowing patient stratification for future treatment strategies.
Comparison of whole brain radiation therapy for synchronous brain metastases with irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases to boost irradiation in the treatment of brain metastases from SCLC: study protocol for a randomized controlled trial
Authors: Zhang Xiaofang , Wang Tianlu , Wang Chen Yu , Zhao Peng , Huang Bo , He Lei , Song Ying Qiu 
Published: October 2022

Abstract
Background
This study is in regard to the comparison of whole brain radiation therapy for synchronous brain metastases with irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases to boost irradiation in the treatment of brain metastases from small cell lung cancer (SCLC). Therapeutically, they have notably varying dose distributions. Based on theoretical and model studies, it has long been speculated that these modes may result in different prognostic outcomes. We aim to assess the efficacy of tomotherapy in the treatment of SCLC brain metastases while protecting the key functional area, the hippocampus, and minimizing any neurocognitive impairments incurred by radiation.

Methods
This is a randomized, controlled, prospective study including 102 SCLC patients with brain metastases randomized (1:1) to the experimental (whole brain radiation therapy for synchronous brain metastases with irradiation to protect the hippocampus) or control (whole brain radiotherapy for sequential brain metastases to boost irradiation) group. The sample size is calculated through a single-sided test; 102 participants will be required for the main results to have statistical and clinical significance. We aim to provide clinical trial data support for better prognostic treatment options in patients with SCLC and brain metastases. The clinical trial data include both the primary and secondary outcomes; the primary outcome is the intracranial progression-free survival time after the new technology application. The secondary study outcomes include the assessment of neurological function, the quality of life, and the overall survival rate. Follow-up consultations will be conducted every 2 months. After the final patient completes follow-up, the Statistical Product and Service Solutions software will be used for scientific and rigorous data analysis. Version 1.0 of the protocol was implemented on January 1, 2021; the recruitment process for this clinical trial commenced on April 1, 2021, and will end on March 31, 2024.

Discussion
The study will provide high-quality clinical evidence to support the efficacy and safety of whole brain radiation therapy for synchronous brain metastases with dose irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases with push volume irradiation for the treatment of patients who have lung cancer as well as brain metastases. This has not been previously reported.

Trial registration
This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900027539; November 17, 2019) (URL: https://www.chictr.org.cn/hvshowproject.aspx?id=20515).
The effect of an 8-week treatment program using a novel foot neuromuscular electrical stimulator on physical function, leg pain, leg symptoms, and leg blood flow in community-dwelling older adults: a randomized sham-controlled trial
Authors: Kumaran Binoy , Targett Darren , Watson Tim 
Published: October 2022

Abstract

Background

Neuromuscular electrical stimulation (NMES) is an established therapy that has been widely used for many decades to improve circulation in the legs. However, studies using NMES devices in an elderly, ambulant, and otherwise apparently healthy population are lacking; this is despite the use of such devices being indicated for lower leg symptoms (such as aches, pain, and cramps) that are frequently seen in older individuals. The main purpose of this study is to evaluate the effect of non-invasive foot NMES (administered using Revitive Medic©) on such symptoms compared to a sham in a 12-week period.

Methods
This is a single-center, single (participant)-blind, parallel-group, randomized, placebo-controlled (sham group), interventional study. Participants will be randomized to 1 of 3 groups (1:1:1) with each study group receiving a different type of foot NMES: Revitive sham; Revitive Medic© Program 1; or Revitive® Program 2. Each participant will be instructed to self-administer the foot NMES device for 30 min twice daily for 8 weeks. During the study, all participants will continue with their normal life, activities, medications, and diet with no restrictions. Following the 8-week NMES treatment program participants will be assessed for Canadian Occupational Performance Measure performance (COPM-P) and satisfaction (COPM-S) scores, lower leg pain, lower leg symptoms (heaviness, tiredness, aching and cramps), and blood flow volume and intensity.

Discussion
Revitive® foot NMES has been proven to increase blood circulation in the legs during use, which may help to relieve symptoms such as pain, heaviness, cramps, and tiredness. When NMES is applied to the plantar surface of the feet it indirectly induces contraction of the calf muscle, activating the musculo-venous pump and thus improving circulation. This study aims to provide data informing on the applicability of foot NMES for the management of leg symptoms that are likely to be indicative of poor circulation in an elderly (> 65 years) community population.

Trial registration
ISRCTN10576209.
Restored intestinal integrity, nutrients transporters, energy metabolism, antioxidative capacity and decreased harmful microbiota were associated with IUGR piglet's catch-up growth before weanling
Authors: Cui Chang , Wu Caichi , Wang Jun , Ma Ziwei , Zheng Xiaoyu , Zhu Pengwei , Wang Nuan , Zhu Yuhua , Guan Wutai , Chen Fang 
Published: October 2022

Abstract
Background
Intrauterine growth restriction (IUGR) is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth (CUG) before weanling could significantly restore this negative influence. But there was limited knowledge about the underlying mechanism of CUG occurrence.

Methods
Eighty litters of newborn piglets were divided into normal birth weight (NBW) and IUGR groups according to birth weight. At 26 d, those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG, and the piglets with IUGR still below average body weight were considered as NCUG. This study was conducted to systemically compare the intestinal difference among NBW, CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.

Results
The results indicated that the mRNA expression of nutrients (amino acids, glucose, and fatty acids) transporters, and mitochondrial electron transport chain (ETC) I were upregulated in CUG piglets’ gut with improved morphology compared with those NCUG, as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism. Meanwhile, CUG piglet’s gut showed higher antioxidative capacity with increased SOD and GSH-Px activity, decreased MDA levels, as well as higher mRNA expressions of Nrf2, Keap1, SOD, and GSH-Px. Furthermore, inflammatory parameters including TNF-α, IL-1β, IL-6, and IL-12 factors, and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine, while the protein expression of ZO-1, Occludin and Claudin-1 was reduced. The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets, and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.

Conclusions
CUG piglet’s intestine showed comprehensive restoration including higher nutrients transport, energy metabolism, antioxidant capacity, and intestinal physical barrier, while lower oxidative stress, inflammatory response, and pathogenic microbiota.
Characteristics of physical properties of the sliding and its surrounding layers in landslides caused by the 2018 Hokkaido Eastern Iburi Earthquake
Authors: Istiyanti Mega Lia , Goto Satoshi 
Published: October 2022

AbstractA 6.6-Mw earthquake struck the Iburi region of Hokkaido, Japan, in 2018, triggering massive landslides. Most of these landslides were shallow and occurred mostly in the Atsuma and Abira towns. Ta-c and Ta-d tephra layers have been found in the Towa landslide at Atsuma from the Tarumai volcano, while Ta-d, En-a, and Spfa-1 tephra layers have been found in the Mizuho landslide at Abira from the Tarumai and Eniwa volcanos, as well as the Shikotsu caldera. Field observations from previous studies revealed that the sliding layers were located in the Ta-d and En-a layers at the Towa and Mizuho landslides, respectively. Unlike previous research on earthquake-induced landslides, which were investigated using mechanical properties, this study investigates the characteristics of physical properties, saturated permeability properties, and content of clay minerals on sliding and surrounding tephra layers. Results from this study reveal that the physical properties of sliding layers from two landslides demonstrated the same characteristics: non-plastic soil with a low density of soil particles, void ratio, and dry density; these characteristics could influence earthquake-induced landslides. It also reveals a relationship between the plasticity chart and the age of tephra materials, including the relationship between the weathering process and density of soil particles and the dissimilarity in characteristics of saturated permeability properties in tephra materials.
Systemic protothecosis in an immunocompetent patient
Authors: Trespalacios Sierra Alvano , Arroyo-Salgado Bárbara , Rodriguez-Blanco Jesús , Tibocha Gordon Ingrid , Martínez-Ávila María Cristina 
Published: October 2022

AbstractBackgroundAlthough uncommon, there is increasing interest and public health concerns of the pathogenPrototheca spp, a ubiquitous achlorophilic microalgae that can affect both humans and animals. High mortality rates have been reported in immunocompromised patients with disseminated infection, but no data is available in the immunocompetent population.Case PresentationWe present the case of a 59-year-old man from rural area of Colombia who was admitted to the intensive care unit due to decompensated heart failure that was difficult to medically manage, with development of septic shock and isolation ofPrototheca wickerhamiifrom blood culture. Fluconazole and Amphotericin B were given with successful outcome.ConclusionsTo date, protothecosis and its virulence factors and pathogenesis remain to be fully understood, in our case the isolation of this microalga and its implication of exacerbating chronic conditions such as heart failure is unclear. The medical-scientific community is invited to study this microorganism to determine effective management strategies, as well as its timely identification, treatment, and control, to avoid fatal outcomes.