bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing lipid management—impact of the COVID 19 pandemic upon cardiovascular risk in England
Authors: Newton Julia L , Hamed Joseph , Williams Helen , Kearney Matt , Metcalfe Alison M , Ford Gary A 
Published: May 2023

Abstract

Background
We sought to understand the impact of the COVID-19 pandemic on lipid-lowering therapy prescribing as a potential cause of the excess cardiovascular mortality seen post-pandemic in England. We examined temporal changes over 3 years in the prescribing of high-intensity and non-high-intensity statin therapy and ezetimibe.

Sources of data
We utilized data available via the National Health Service (NHS) Business Services Authority (NHSBSA) Information Services Data Warehouse, extracting 3 monthly data from October 2018 to December 2021 on high- and low-intensity statin and ezetimibe prescribing, (commencement, cessation or continuation) through each time period of study and those before, and after, the period of interest.

Areas of agreement
Optimizing lipid management is a key component of the NHS Long Term Plan ambition to reduce deaths from cardiovascular disease, stroke and dementia.

Areas of controversy
The COVID-19 pandemic and associated lockdown have seen a significant reduction in prescribing of lipid-lowering therapies. If cardiovascular risk is not to worsen in the forthcoming years, urgent action is needed to ensure that the impact of the pandemic upon optimization of cholesterol and the historical undertreatment of cholesterol is reversed and improved.

Areas timely for developing research
Prescription data available via NHSBSA can support our understanding of the implications of policy and behaviour and highlight the impact of guidelines in practise.

Growing points
Understanding the impact of the COVID-19 pandemic upon cholesterol management and the opportunities for newer lipid-lowering therapies delivered using a population health approach have the potential to enhance lipid-lowering and improve cardiovascular mortality and morbidity and reduce health inequalities.
Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium
Authors: Chen Wanchao , Wang Yang , Zheng Jiancheng , Chen Yan , Zhang Can , Yang Wei , Wu Lingling , Yang Zeyu , Wang Yu , Shi Chunmeng 
Published: May 2023

Abstract

Background
Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation. The most important feature of radiation ulcers is progressive ulceration, which results in the expansion of radiation injury to the nonirradiated area and refractory wounds. Current theories cannot explain the progression of radiation ulcers. Cellular senescence refers to as irreversible growth arrest that occurs after exposure to stress, which contributes to tissue dysfunction by inducing paracrine senescence, stem cell dysfunction and chronic inflammation. However, it is not yet clear how cellular senescence facilitates the continuous progression of radiation ulcers. Here, we aim to investigate the role of cellular senescence in promoting progressive radiation ulcers and indicate a potential therapeutic strategy for radiation ulcers.

Methods
Radiation ulcer animal models were established by local exposure to 40 Gy X-ray radiation and continuously evaluated for &gt;260 days. The roles of cellular senescence in the progression of radiation ulcers were assessed using pathological analysis, molecular detection and RNA sequencing. Then, the therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells (uMSC-CM) were investigated in radiation ulcer models.

Results
Radiation ulcer animal models with features of clinical patients were established to investigate the primary mechanisms responsible for the progression of radiation ulcers. We have characterized cellular senescence as being closely associated with the progression of radiation ulcers and found that exogenous transplantation of senescent cells significantly aggravated them. Mechanistic studies and RNA sequencing suggested that radiation-induced senescent cell secretions were responsible for facilitating paracrine senescence and promoting the progression of radiation ulcers. Finally, we found that uMSC-CM was effective in mitigating the progression of radiation ulcers by inhibiting cellular senescence.

Conclusions
Our findings not only characterize the roles of cellular senescence in the progression of radiation ulcers but also indicate the therapeutic potential of senescent cells in their treatment.
International Economic Law in the ‘Asian Century’
Authors: Petersmann Ernst-Ulrich 
Published: May 2023

ABSTRACT
The current non-compliance with United Nations (UN) and World Trade Organization (WTO) agreements protecting transnational public goods, military aggression among WTO members, violent suppression of human and democratic rights, global health pandemics, climate change, ocean pollution, overfishing, and other biodiversity losses reflect ‘governance failures’ (e.g. to limit ‘market failures’) and ‘constitutional failures’ (e.g. to protect human and democratic rights and the sustainable development goals). The geopolitical rivalries among totalitarian governments and democracies render constitutional UN and WTO reforms unlikely. They entail ‘regulatory competition’ (e.g. among neoliberalism, state capitalism, and ordo-liberal constitutionalism) and plurilateral responses aimed at limiting abuses of power (like collective countermeasures against Russia’s illegal wars and war crimes) and at protecting transnational public goods (like plurilateral ‘climate change mitigation clubs’, appeal arbitration among WTO members, regional human rights and security agreements). The power politics disrupting the UN and WTO legal systems is bound to promote regionalization of economic law, re-globalization of supply chains, and geopolitical rivalries resulting from conflicting value priorities and neglect for the human rights underlying the sustainable development goals.
Dipping Titan implants in Irrisept solution (0.05% chlorhexidine gluconate) and exposure to various aerobic, anaerobic, and fungal species
Authors: Karpman Edward , Griggs Ryan , Twomey Carolyn , Henry Gerard D 
Published: May 2023

Abstract

Background
The organisms causing penile implant infections are changing from predominantly indolent gram-positive infections to more aggressive gram-negative and fungal infections because of antibiotic selection pressures based on novel next-generation sequencing DNA data.

Aim
To evaluate the effectiveness of Irrisept solution (0.05% chlorhexidine gluconate) in decreasing isolate colony counts from a Titan implant by using a novel kill time washout methodology to mirror real-world usage.

Methods
Sterilized Titan discs were dipped in Irrisept or saline. An inoculum of 109 organisms of a single bacterial or fungal species was placed on the discs. Bacterial and fungal strains were tested: Bacteroides fragilis, Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. The discs were then irrigated 3 times with Irrisept or saline. Microorganisms were sonicated off the discs and placed on appropriate agar and conditions for each species. The plates were incubated for 48 to 72 hours at the temperature and under the conditions appropriate for each species. Colonies on the plates were hand counted.

Outcomes
Irrisept effectively decreased microbial colony counts in all the species tested.

Results
Irrisept was shown to effectively decrease microbial colony counts from 3 to 6 log10 in all species tested. A 3-log10 reduction is considered the target level of performance that would indicate that a compound or product has effective killing activity against an organism of interest. The saline control with bulb syringe irrigation did not demonstrate reduction of microbial colony counts in any of the species tested.

Clinical Implications
Irrisept is effective against all of the organisms causing modern-day infections with penile implant surgery and may decrease clinical infection rates to lower levels.

Strengths and Limitations
The strength of this study is that we used quantitative microbial reduction counting and the largest array of bacterial and fungal species causing modern-day penile implant infections. The limitation is that this is an in vitro study and the clinical implications of our findings are not yet known.

Conclusion
Quantitative microbial reduction counting shows that Irrisept is effective against the most commonly known modern-day organisms causing penile implant infections.
Infections transmitted via the faecal–oral route: a simple score for a global risk map
Authors: Stürchler Dieter 
Published: May 2023

Abstract

Introduction
Faecal-oral transmission refers to the process whereby disease is transmitted via the faeces of an infected individual to the mouth of a susceptible individual. This transmission can occur through failures in sanitation systems leading to exposure via various routes in particular contaminated water, food, and hands. Travellers’ diarrhoea is the most common travel-related illness. A score could enhance risk assessment and pre-travel advice.

Methods
A simple score was developed based on the frequency of defecating in the open (country prevalence &gt; 1%), occurrence of cholera in the period between 2021 and 2017 (one or more case in a country) and reported typhoid fever cases between 2015 and 2019.

Results
Data were available for 199 out of 214 countries for the score to be applied. 19% of the 199 countries scored as high risk countries for faecal-oral transmission (score 3), 47% as medium risk (score 2), and 34% as minimal risk (score 0). The percentage of countries scoring 3 was highest in Africa (63%) and lowest in Europe and Oceania (score 0).

Conclusions
A global risk map was developed based on a simple score that could aid travel medicine providers in providing pre-travel risk assessment. For travellers to high and medium risk countries, pre-travel consultation must include detailed advice on food and water hygiene.
Mid- and far-infrared spectroscopy of nucleobases: molar extinction coefficients, integrated molar absorptivity, and temperature dependence of the main bands
Authors: Iglesias-Groth Susana , Cataldo Franco 
Published: May 2023

ABSTRACT
The nucleobases, namely the purines adenine and guanine and the pyrimidines cytosine, thymine, and uracil, are the key monomers of the information polymers DNA and RNA. All the nucleobases were recently detected in the analysis of certain meteorites known as carbonaceous chondrites. The concentration of the nucleobases found in meteorites is smaller than the concentration of amino acids. However, the nucleobases were successfully synthesized abiotically by ultraviolet irradiation of interstellar ice analogues at 10 K. Consequently, it is possible that the purines and pyrimidines may be present in the interstellar medium or in other space environments and may be detectable by the new orbiting telescopes that indeed are able to cover not only the mid-infrared spectral range but also the far-infrared. This work supplies the reference spectra of the five nucleobases used by the terrestrial biochemistry in the mid-infrared and in the far-infrared with the purpose to facilitate the search and identification of these astrobiological and astrochemical relevant molecules in space. The mid-infrared spectra of all nucleobases were recorded at three different temperatures from −180 °C to nearly ambient temperature and at +250 °C. Furthermore, the molar extinction coefficients (ε) of all mid- and far-infrared bands were determined, as well as the integrated molar absorptivities (ψ). With the reported infrared spectra together with the ε and ψ values, it will be possible to identify qualitatively the nucleobases and estimate their relative abundance in space.
The ribosome quality control factor Asc1 determines the fate of HSP70 mRNA on and off the ribosome
Authors: Alagar Boopathy Lokha R , Beadle Emma , Xiao Alan RuoChen , Garcia-Bueno Rico Aitana , Alecki Celia , Garcia de-Andres Irene , Edelmeier Kyla , Lazzari Luca , Amiri Mehdi , Vera Maria 
Published: May 2023

Abstract
Cells survive harsh environmental conditions by potently upregulating molecular chaperones such as heat shock proteins (HSPs), particularly the inducible members of the HSP70 family. The life cycle of HSP70 mRNA in the cytoplasm is unique—it is translated during stress when most cellular mRNA translation is repressed and rapidly degraded upon recovery. Contrary to its 5′ untranslated region's role in maximizing translation, we discovered that the HSP70 coding sequence (CDS) suppresses its translation via the ribosome quality control (RQC) mechanism. The CDS of the most inducible Saccharomyces cerevisiae HSP70 gene, SSA4, is uniquely enriched with low-frequency codons that promote ribosome stalling during heat stress. Stalled ribosomes are recognized by the RQC components Asc1p and Hel2p and two novel RQC components, the ribosomal proteins Rps28Ap and Rps19Bp. Surprisingly, RQC does not signal SSA4 mRNA degradation via No-Go-Decay. Instead, Asc1p destabilizes SSA4 mRNA during recovery from heat stress by a mechanism independent of ribosome binding and SSA4 codon optimality. Therefore, Asc1p operates in two pathways that converge to regulate the SSA4 mRNA life cycle during stress and recovery. Our research identifies Asc1p as a critical regulator of the stress response and RQC as the mechanism tuning HSP70 synthesis.
AT-specific DNA visualization revisits the directionality of bacteriophage λ DNA ejection
Authors: Bong Serang , Park Chung Bin , Cho Shin-Gyu , Bae Jaeyoung , Hapsari Natalia Diyah , Jin Xuelin , Heo Sujung , Lee Ji-eun , Hashiya Kaori , Bando Toshikazu , Sugiyama Hiroshi , Jung Kwang-Hwan , Sung Bong June , Jo Kyubong 
Published: May 2023

Abstract
In this study, we specifically visualized DNA molecules at their AT base pairs after in vitro phage ejection. Our AT-specific visualization revealed that either end of the DNA molecule could be ejected first with a nearly 50% probability. This observation challenges the generally accepted theory of Last In First Out (LIFO), which states that the end of the phage λ DNA that enters the capsid last during phage packaging is the first to be ejected, and that both ends of the DNA are unable to move within the extremely condensed phage capsid. To support our observations, we conducted computer simulations that revealed that both ends of the DNA molecule are randomized, resulting in the observed near 50% probability. Additionally, we found that the length of the ejected DNA by LIFO was consistently longer than that by First In First Out (FIFO) during in vitro phage ejection. Our simulations attributed this difference in length to the stiffness difference of the remaining DNA within the phage capsid. In conclusion, this study demonstrates that a DNA molecule within an extremely dense phage capsid exhibits a degree of mobility, allowing it to switch ends during ejection.
Realism and the Value of Explanation
Authors: Andrews Samuel John 
Published: May 2023

Abstract
Dasgupta poses a serious challenge to realism about natural properties. He argues that there is no acceptable explanation of why natural properties deserve the value realists assign to them and are consequently absent of value. In response, this paper defines and defends an alternative non-explanatory account of normativity compatible with realism. Unlike Lewis and Sider, who believe it is sufficient to defend realism solely on realist terms, I engage with the challenge on unfriendly grounds by revealing a tu quoque. Dasgupta and anti-realists face a similar challenge to that directed against realism: one that not only undermines the objection to realism by legitimising non-explanatory normativity but leaves them facing a significant dilemma.
An Analysis of Medical Malpractice Litigation due to Intravenous Steroid Treatment for Acute Spinal Cord Injury
Authors: Razzouk Jacob , Mehta Shaurya , Ramos Omar , Danisa Olumide , Cheng Wayne 
Published: May 2023

Study Design:
Retrospective cohort study.

Objective:
To evaluate the incidence of litigation due to using or foregoing methylprednisolone (MP), naloxone, or tirilazad for treatment of acute spinal cord injury (ASCI) through querying the Westlaw and VerdictSearch databases.

Summary of Background Data:
There is historic controversy regarding the use of intravenous steroids for treatment of ASCI. Many highlight that MP continues to be used for ASCI treatment mainly as a defensive medicine tactic due to the fear of malpractice litigation.

Methods:
Westlaw and VerdictSearch were queried for cases involving steroid treatment for ASCI between the years 1998 and 2021. Collected data for each case included year of case hearing, verdict ruling, location of filed claim, and the plaintiff’s basis of litigation. Cases were reviewed and categorized by two independent reviewers based on the grievance(s) levied by the plaintiff. Inclusion criteria for topic relevance was defined as a plaintiff’s basis of litigation resting on a claim of medical malpractice due to the use, or lack thereof, of MP, naloxone, or tirilazad for treatment of ASCI.

Results:
Upon review of 238 cases, case claims were grouped into five categories based on reason for litigation: Social Security benefits (171), lawsuit due to vaccination (25), medical malpractice unrelated to steroid use (16), fungal infections due to MP injections (4), and other (22). Zero cases were found to be related to lawsuits filed due to steroid use or lack thereof for ASCI treatment.

Conclusion:
Our findings suggest there is limited risk of malpractice litigation due to steroid use or lack thereof in the treatment of ASCI. As such, steroid-related treatment decisions for ASCI should be informed by evidence-based approaches to care not influenced by medicolegal concerns.
Ninety Percent of Patients Are Satisfied With Their Decision to Undergo Spine Surgery for Degenerative Conditions
Authors: Maayan Omri , Shahi Pratyush , Merrill Robert K. , Pajak Anthony , Lu Amy Z. , Oquendo Yousi , Subramanian Tejas , Araghi Kasra , Tuma Olivia C. , Korsun Maximilian K. , Asada Tomoyuki , Singh Nishtha , Singh Sumedha , Sheha Evan D. , Dowdell James E. , Qureshi Sheeraz A. , Iyer Sravisht 
Published: May 2023

Study Design.
Cross-sectional survey and retrospective review of prospectively collected data.

Objective.
To explore how patients perceive their decision to pursue spine surgery for degenerative conditions and evaluate factors correlated with decisional regret.

Summary of Background Data.
Prior research shows that one-in-five older adults regret their decision to undergo spinal deformity surgery. However, no studies have investigated decisional regret in patients with degenerative conditions.

Methods.
Patients who underwent cervical or lumbar spine surgery for degenerative conditions (decompression, fusion, or disk replacement) between April 2017 and December 2020 were included. The Ottawa Decisional Regret Questionnaire was implemented to assess prevalence of decisional regret. Questionnaire scores were used to categorize patients into low (<40) or medium/high (≥40) decisional regret cohorts. Patient-reported outcome measures (PROMs) included the Oswestry Disability Index, Patient-reported Outcomes Measurement Information System, Visual Analog Scale (VAS) Back/Leg/Arm, and Neck Disability Index at preoperative, early postoperative (<6 mo), and late postoperative (≥6 mo) timepoints. Differences in demographics, operative variables, and PROMs between low and medium/high decisional regret groups were evaluated.

Results.
A total of 295 patients were included (mean follow-up: 18.2 mo). Overall, 92% of patients agreed that having surgery was the right decision, and 90% would make the same decision again. In contrast, 6% of patients regretted the decision to undergo surgery, and 7% noted that surgery caused them harm. In-hospital complications (P=0.02) and revision fusion (P=0.026) were significantly associated with higher regret. The medium/high decisional regret group also exhibited significantly worse PROMs at long-term follow-up for all metrics except VAS-Arm, and worse achievement of minimum clinically important difference for Oswestry Disability Index (P=0.007), Patient-Reported Outcomes Measurement Information System (P<0.0001), and VAS-Leg (P<0.0001).

Conclusions.
Higher decisional regret was encountered in the setting of need for revision fusion, increased in-hospital complications, and worse PROMs. However, 90% of patients overall were satisfied with their decision to undergo spine surgery for degenerative conditions. Current tools for assessing patient improvement postoperatively may not adequately capture the psychosocial values and patient expectations implicated in decisional regret.
Trimetazidine Affects Mitochondrial Calcium Uniporter Expression to Restore Ischemic Heart Function via Reactive Oxygen Species/NFκB Pathway Inhibition
Authors: Xiao Zilong , Guan Lichun , Shi Hui , Yu Yong , Yu Ziqing , Qin Shengmei , Su Yangang , Chen Ruizhen , Li Minghui , Ge Junbo 
Published: May 2023

Abstract:
Studies have demonstrated the roles of trimetazidine beyond being an antianginal agent in ischemic heart disease (IHD) treatment associated with mechanisms of calcium regulation. Our recent studies revealed that mitochondrial calcium uniporter (MCU, the pore-forming unit responsible for mitochondrial calcium entrance) inhibition provided cardioprotective effects for failing hearts. Because trimetazidine and MCU are associated with calcium homeostasis, we hypothesized that trimetazidine may affect MCU to restore the failing heart function. In the present study, we tested this hypothesis in the context of cardiac ischemia in vivo and in vitro. The IHD model was established in male C57BL/6 mice followed by trimetazidine administration intraperitoneally at 20 mg/kg q.o.d for 8 weeks. In vitro studies were performed in a hypoxia model using primary rat neonate cardiomyocytes. The mice survival outcomes and heart function, pathohistologic, and biological changes were analyzed. The results demonstrated that trimetazidine treatment resulted in longer life spans and heart function improvement accompanied by restoration of mitochondrial calcium levels and increase in ATP production via MCU down-regulation. Studies in vitro further showed that trimetazidine treatment and MCU inhibition decreased reactive oxygen species (ROS) production, inhibited the NFκB pathway, and protected the cardiomyocytes from hypoxic injury, and vice versa. Thus, the present study unveils a unique mechanism in which trimetazidine is involved in ameliorating the ischemic failing heart via MCU down-regulation and the following mitochondrial calcium homeostasis restoration, ROS reduction, and cardiomyocyte protection through NFκB pathway inhibition. This mechanism provides a novel explanation for the treatment effects of trimetazidine on IHD.