bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-Way Cell-Based Screening of Antistress Compounds: Identification, Validation, and Relevance to Old-Age-Related Pathologies
Authors: Zhang Huayue , Wang Jia , Prakash Jay , Zhang Zhenya , Kaul Sunil C , Wadhwa Renu 
Published: April 2023

Abstract
A variety of environmental stress stimuli have been linked to poor quality of life, tissue dysfunctions, and ailments including metabolic disorders, cognitive impairment, and accelerated aging. Oxidative, metal, and hypoxia stresses are largely associated with these phenotypes. Whereas drug development and disease therapeutics have advanced remarkably in last 3 decades, there are still limited options for stress management. Because the latter can effectively decrease the disease burden, we performed cell-based screening of antistress compounds by recruiting 3 chemical models of oxidative (paraquat), metal (cadmium nitrate), or hypoxia (cobalt chloride) stresses. The screening of 70 compounds for their ability to offer protection against oxidative, metal, and hypoxia stresses resulted in the selection of 5 compounds: Withaferin-A (Wi-A), methoxy Withaferin-A (mWi-A), Withanone (Wi-N), triethylene glycol (TEG), and Ashwagandha (Withania somnifera) leaf M2-DMSO extract (M2DM). Molecular assays revealed that whereas stress caused increase in (a) apoptosis, (b) reactive oxygen species accumulation coupled with mitochondrial depolarization, (c) DNA double-strand breaks, and (d) protein aggregation, low nontoxic doses of the selected compounds caused considerable protection. Furthermore, Wi-N, TEG, and their mixture-treated normal human fibroblasts (at young, mature, and senescent stages representing progressively increasing accumulation of stress) showed increase in proliferation. Taken together, these results suggested 3-way (oxidative, metal, and hypoxia) antistress potential of Wi-N and TEG that may be useful for management of environmental and old-age–related pathologies.
Dynapenic Abdominal Obesity Increases Risk for Falls Among Adults Aged ≥50 Years: A Prospective Analysis of the Irish Longitudinal Study on Ageing
Authors: Smith Lee , López Sánchez Guillermo F , Veronese Nicola , Soysal Pinar , Rahmati Masoud , Jacob Louis , Kostev Karel , Haro Josep Maria , Alghamdi Abdullah Ahmed , Butler Laurie , Barnett Yvonne , Keyes Helen , Tully Mark A , Shin Jae Il , Koyanagi Ai 
Published: April 2023

Abstract

Background
There is a scarcity of studies examining the longitudinal relationship between dynapenic abdominal obesity (DAO; ie, impairment in muscle strength and high waist circumference) and future fall risk. Therefore, we aimed to investigate the prospective association between DAO at baseline and falls occurring during 2 years of follow-up in a nationally representative sample of middle-aged and older individuals from Ireland.

Methods
Data from 2 consecutive waves of the Irish Longitudinal Study on Ageing survey were analyzed. Dynapenia was defined as handgrip strength of &lt;26 kg for men and &lt;16 kg for women. Abdominal obesity was defined as a waist circumference of &gt;88 cm for women and &gt;102 cm for men. DAO was assessed at Wave 1 (2009–2011) and was defined as having both dynapenia and abdominal obesity. Falls occurring between Wave 1 and Wave 2 (2012–2013) were self-reported. Multivariable logistic regression analysis was conducted.

Results
Data on 5 275 individuals aged ≥50 years were analyzed (mean [standard deviation {SD}] age 63.2 [8.9] years; 48.8% males). After adjustment for potential confounders, compared to no dynapenia and no abdominal obesity at baseline, DAO was significantly associated with 1.47 (95% confidence interval [CI]: 1.14–1.89) times higher odds for falls at 2-year follow-up. Dynapenia alone (odds ratio [OR] = 1.08; 95% CI: 0.84–1.40) and abdominal obesity alone (OR = 1.09; 95% CI: 0.91–1.29) were not significantly associated with falls at follow-up.

Conclusions
DAO increased the risk for falls among middle-aged and older adults in Ireland. Interventions to prevent or reverse DAO may be beneficial for fall reduction.
Licensing libel in seventeenth-century England: John White’s First Century of Scandalous, Malignant Priests in context/s
Authors: Fullerton Samuel 
Published: April 2023

Abstract
This article explores the polemical history of John White’s First Century of Scandalous, Malignant Priests (1643) to argue that the revolutionary public culture of England’s mid-century civil wars transformed seventeenth-century libellous politics by rendering ad hominem defamation into a routine element of formal partisan print culture for the first time in English history. The article concludes by demonstrating that when the Century reappeared in print eighty years later to excoriate a new generation of clergymen, public defamation had become a mundane, although still controversial, element of English political culture.
Chromosomal microdeletion leading to pituitary gigantism through hormone-gene overexpression
Authors: Katoh-Fukui Yuko , Hattori Atsushi , Zhang Ruogu , Terao Miho , Takada Shuji , Nakabayashi Kazuhiko , Hata Kenichiro , Yamada Yutaka , Matsuura Nobuo , Fukami Maki 
Published: April 2023

Abstract
Pituitary gigantism is a rare endocrinopathy characterized by tall stature due to growth hormone (GH) hypersecretion. This condition is generally linked to a genetic predisposition to tumors that produce GH or GH-releasing hormone (GHRH). Here, we report a Japanese woman who exhibited prominent body growth from infancy to reach an adult height of 197.4 cm (+7.4 standard deviation). Her blood GH levels were markedly elevated. She carried no pathogenic variants in known growth-controlling genes but had a hitherto unreported 752 kb heterozygous deletion at 20q11.23. The microdeletion was located 8.9 kb upstream of GHRH and encompassed exons 2–9 of a ubiquitously expressed gene TTI1 together with 12 other genes, pseudogenes and non-coding RNAs. Transcript analyses of the patient’s leukocytes showed that the microdeletion produced chimeric mRNAs consisting of exon 1 of TTI1 and all coding exons of GHRH. In silico analysis detected promoter-associated genomic features around TTI1 exon 1. Genome-edited mice carrying the same microdeletion recapitulated accelerated body growth from a few weeks after birth. The mutant mice developed pituitary hyperplasia and exhibited ectopic Ghrh expression in all tissues examined. Thus, the extreme phenotype of pituitary gigantism in the patient likely reflects GHRH overexpression driven by an acquired promoter. The results of this study indicate that germline submicroscopic deletions have the potential to cause conspicuous developmental abnormalities due to gene overexpression. Furthermore, this study provides evidence that constitutive expression of a hormone-encoding gene can result in congenital disease.
Modelled dispersal of snow crab (Chionoecetes opilio) larvae and potential settlement areas in the western Barents Sea
Authors: Huserbråten M , Hjelset A M , Danielsen H E H , Hvingel C , Agnalt A-L 
Published: April 2023

Abstract
Since the mid-1990s, a snow crab (Chionoecetes opilio) population has established in the eastern Barents Sea. Spawning females and newly hatched larvae are now also found in the central Barents Sea, warranting speculations on a further westward colonization by pelagic larvae. Here, we model the potential for larval dispersal and settlement into uncolonized areas in the western Barents Sea. We used a biophysical model of ocean currents and hydrography, coupled with a Lagrangian dispersal algorithm and larval survival functions as response to temperature. The model predicts limited dispersal from the central Barents Sea to western areas, primarily due to a mismatch between prevailing temperature regimes and temperature tolerances for the different larval stages. In addition, there was limited westward transport of water masses with temperatures that would allow completion of the pelagic larval development. We speculate that for larvae to successfully supply benthic recruits to the remaining uncolonized areas in the western Barents Sea, adult crabs would first need to establish new spawning aggregations, for example along the western slopes of the Barents Sea shelf. Immediate implications are limited potential for expanding the fishery to the western areas of the Barents Sea.
Development of an in vitro pharmacokinetic/pharmacodynamic model in the presence of serum for studying micafungin activity against Candida albicans: a need for revision of CLSI susceptibility breakpoints
Authors: Beredaki Maria-Ioanna , Arendrup Maiken C , Andes David , Meletiadis Joseph 
Published: April 2023

Abstract

Background
The CLSI breakpoint for micafungin and Candida albicans is 0.25 mg/L, higher than the CLSI epidemiological cut-off value (0.03 mg/L) whereas the EUCAST values are identical (0.016 mg/L). We developed a novel in vitro dialysis-diffusion pharmacokinetic/pharmacodynamic (PK/PD) model, confirmed correlation to in vivo outcome and studied micafungin pharmacodynamics against Canida albicans.

Methods
Four C. albicans isolates, including a weak (F641L) and a strong (R647G) fks1 mutants, were studied using a 104 cfu/mL inoculum and RPMI medium with and without 10% pooled human serum. The exposure-effect relationship fAUC0–24/MIC was described for CLSI and EUCAST methodology. Monte Carlo simulation analysis included standard (100 mg i.v.) and higher (150–300 mg) doses q24h to determine the corresponding probability of target attainment (PTA).

Results
The in vitro PK/PD targets for stasis/1-log kill were 36/57 fAUC0–24/MIC in absence and 2.8/9.2 fAUC0–24/MIC in the presence of serum, and similar for wild-type and fks mutant isolates. The PTAs for both PK/PD targets were high (&gt;95%) for EUCAST susceptible isolates but not for CLSI susceptible non-wild-type isolates (CLSI MICs 0.06–0.25 mg/L). 300 mg q24h was needed to attain PK/PD targets for non-wild-type isolates with CLSI MICs 0.06–0.125 mg/L and EUCAST MICs 0.03–0.06 mg/L.

Conclusion
The in vitro 1-log kill effect corresponded to stasis in animal model and mycological response in patients with invasive candidiasis, thereby validating the model for studying pharmacodynamics of echinocandins in vitro. EUCAST breakpoints were well supported by our findings but our data questions whether the current CLSI breakpoint, which is higher than the epidemiological cut-off values, is appropriate.
Animal pharmacokinetics/pharmacodynamics (PK/PD) infection models for clinical development of antibacterial drugs: lessons from selected cases
Authors: Moore Jason N , Poon Lucas , Pahwa Sonia , Bensman Timothy , Wei Xiaohui (Tracey) , Danielsen Zhixia Yan , Jang Seong 
Published: April 2023

Abstract
In the wake of emerging antimicrobial resistance, antibacterial drug development has become more critical. At the same time, development of antibacterial drugs targeting specific pathogens or resistance phenotypes that may have low prevalence presents challenges because it is difficult to conduct large, randomized controlled trials for such drugs. Animal models have increasingly supported clinical development of antibacterials; however, more work is needed to optimize the design and application of these animal models to ensure clear and actionable translation to further human investigation. This review discusses recent case studies of animal infection models used to support antibacterial drug development in order to illuminate considerations for future development of novel antibacterial drugs.
Lytic bacteriophage vB_KmiS-Kmi2C disrupts biofilms formed by members of the Klebsiella oxytoca complex, and represents a novel virus family and genus
Authors: Newberry Fiona , Shibu Preetha , Smith-Zaitlik Thomas , Eladawy Mohamed , McCartney Anne L , Hoyles Lesley , Negus David 
Published: April 2023

Abstract

Aims
This study aimed to characterize the lytic phage vB_KmiS-Kmi2C, isolated from sewage water on a GES-positive strain of Klebsiella michiganensis.

Methods and Results
Comparative phylogenetic and network-based analyses were used to characterize the genome of phage vB_KmiS-Kmi2C (circular genome of 42 234 bp predicted to encode 55 genes), demonstrating it shared little similarity with other known phages. The phage was lytic on clinical strains of K. oxytoca (n = 2) and K. michiganensis (n = 4), and was found to both prevent biofilm formation and disrupt established biofilms produced by these strains.

Conclusions
We have identified a phage capable of killing clinically relevant members of the K. oxytoca complex (KoC). The phage represents a novel virus family (proposed name Dilsviridae) and genus (proposed name Dilsvirus).
More than algorithms: an analysis of safety events involving ML-enabled medical devices reported to the FDA
Authors: Lyell David , Wang Ying , Coiera Enrico , Magrabi Farah 
Published: April 2023

Abstract

Objective
To examine the real-world safety problems involving machine learning (ML)-enabled medical devices.

Materials and Methods
We analyzed 266 safety events involving approved ML medical devices reported to the US FDA’s MAUDE program between 2015 and October 2021. Events were reviewed against an existing framework for safety problems with Health IT to identify whether a reported problem was due to the ML device (device problem) or its use, and key contributors to the problem. Consequences of events were also classified.

Results
Events described hazards with potential to harm (66%), actual harm (16%), consequences for healthcare delivery (9%), near misses that would have led to harm if not for intervention (4%), no harm or consequences (3%), and complaints (2%). While most events involved device problems (93%), use problems (7%) were 4 times more likely to harm (relative risk 4.2; 95% CI 2.5–7). Problems with data input to ML devices were the top contributor to events (82%).

Discussion
Much of what is known about ML safety comes from case studies and the theoretical limitations of ML. We contribute a systematic analysis of ML safety problems captured as part of the FDA’s routine post-market surveillance. Most problems involved devices and concerned the acquisition of data for processing by algorithms. However, problems with the use of devices were more likely to harm.

Conclusions
Safety problems with ML devices involve more than algorithms, highlighting the need for a whole-of-system approach to safe implementation with a special focus on how users interact with devices.
Our epistemic dependence on others: Nyāya and Buddhist accounts of testimony as a source of knowledge
Authors: Picascia Rosanna 
Published: April 2023

Abstract
This paper argues that philosophical debates between Nyāya and Buddhists on the nature and acquisition of testimonial knowledge present contrasting images of the role played by the epistemic agent in the knowing process. According to Nyāya, an individual can acquire testimonial knowledge automatically—and with little epistemic work—from a trustworthy speaker’s say-so. On the other hand, Buddhist epistemologists, who claim that testimonial knowledge is a species of inferential knowledge, argue that, in order to acquire knowledge from a speaker’s statements, an epistemic agent must possess non-testimonial evidence for the reliability of the testimony in question. This disagreement regarding the division of epistemic labour in testimonial exchanges demonstrates how differently Nyāya and Buddhist philosophers view the prevalence and practical importance of testimonial knowledge. For Nyāya, the ubiquity and easy acquisition of testimonial knowledge help explain the success of our daily actions. However, for Buddhist epistemologists, despite the regularity with which we successfully act based on what others tell us, testimonial knowledge is, in fact, less common, and more difficult to acquire, than we might think.
Ensemble species distribution modeling ofCulex tarsalis(Diptera: Culicidae) in the continental United States
Authors: Rhodes Charlotte G , Chaves Luis F , Bergmann Luke R , Hamer Gabriel L 
Published: April 2023

AbstractWest Nile virus (WNV) is the primary mosquito-borne disease in the United States and has had case reports every year since its introduction in 1999. As such, it is critical that we characterize the distribution of WNV vectors. Estimates of Culex tarsalis Coquillett species distribution, a major WNV vector, are scarce. We used ensemble distribution modeling to estimate habitat suitability for this species across the contiguous United States by consolidating presence data from four publicly available mosquito trapping data servers. The central plains region and much of the western US were estimated to have high habitat suitability. We identified multiple metrics of temperature and precipitation to be important in predicting the occurrence of Cx. tarsalis in a given geographic area. Furthermore, we observed habitat suitability for Cx. tarsalis to be significantly higher in areas with a high incidence of West Nile neuroinvasive disease compared to areas with low WN disease incidence, suggesting that Cx. tarsalis is present in regions with a high incidence of disease.
The Scourges: Why Abortion Is Even More Morally Serious than Miscarriage
Authors: Miller Calum 
Published: April 2023

Abstract
Several recent papers have suggested that the pro-life view entails a radical, implausible thesis: that miscarriage is the biggest public health crisis in the history of our species and requires radical diversion of funds to combat. In this paper, I clarify the extent of the problem, showing that the number of miscarriages about which we can do anything morally significant is plausibly much lower than previously thought, then describing some of the work already being done on this topic. I then briefly survey a range of reasons why abortion might be thought more serious and more worthy of prevention than miscarriage. Finally, I lay out my central argument: that reflection on the wrongness of killing reveals that the norms for ending life and failing to save life are different, in such a way that could justify the prioritization of anti-abortion advocacy over anti-miscarriage efforts. Such an account can also respond to similar problems posed to the pro-lifer, such as the question of whom to save in a “burning lab” type scenario.
Predicting the potential value of the new discharge medicines service in England
Authors: Thayer Nick , Mackridge Adam John , White Simon 
Published: April 2023

Abstract

Objectives
In 2021, community pharmacies in England were commissioned to support patients post-discharge through the discharge medicines service (DMS). Past studies described the benefit of DMS in avoiding readmissions. This study aimed to estimate the impact of DMS in this respect, projecting the maximal benefit if all areas mirrored the most active region.

Methods
A retrospective observational study, including modelling, using DMS claims data from March 2021 to February 2022, obtained from the NHS Business Services Authority (data from all community pharmacies in England for patients discharged where hospital clinicians referred them to community pharmacy). The impact of DMS on reducing readmission during this period was estimated using previous study data and estimated maximal benefit from full implementation of the service across England.

Key findings
In the study period 65 634 completed DMS claims were made. Claims at Integrated Care System (ICS) area level varied from 509/10 000 admissions to &lt;1/10 000 admissions. Combining data from past studies provides a relative risk ratio of 0.756 (95% CI 0.678 to 0.843) for 90 day readmission (DMS versus normal care). DMS is estimated to have resulted in 8393 (95% CI 7061 to 9564) fewer readmissions after 30 days reducing to 5869 (95% CI 3774 to 7740) after 90 days. If all-ICS areas were as active as the highest performing area, DMS would avoid estimated &gt;29 000 readmissions at 90 days each year.

Conclusions
DMS has significant potential to reduce readmissions. DMS implementation is currently variable and full implementation across all-ICS areas could increase the benefits five-fold.
Chrysin and its nanoliposome ameliorated non-alcoholic steatohepatitis via inhibiting TLR4 signalling pathway
Authors: Liu Hao , Jiang Ningman , Kuang Ge , Gong Xia , Hu Jun , Liu Jin , Yin Xinru , Wu Shengwang , Wan Jingyuan 
Published: April 2023

Abstract

Objectives
Non-alcoholic steatohepatitis (NASH) is a chronic liver disease histologically characterized by liver steatosis, hepatocellular injury, inflammation and fibrosis, resulting in cirrhosis and hepatocellular carcinoma, but effective measures and obvious pathogenesis for NASH remain elusive. Chrysin (CH) has been reported to have anti-inflammatory effects but shows lower bioavailability.

Methods
In this study, a chrysin nanoliposome (CH-NL) was first prepared and characterized. Then, we used the methionine–choline-deficient (MCD) diet to induce a mouse model of NASH. Finally, the effects of CH and CH-NL on NASH were evaluated in the liver of NASH mice.

Key findings
The results showed that CH or CH-NL significantly reduced the accumulation of lipids in hepatocytes, alleviated liver injury, decreased the generation of radical oxygen species, and attenuated the accumulation of collagen fibre in the liver of NASH mice. In addition, CH and its nano-liposomes markedly inhibited the production of inflammatory cytokines and inflammatory cell infiltration in the liver of NASH mice. Further studies found that CH-NL and CH-NL downregulated the MCD diet-induced activation of Toll-like receptor 4 (TLR4) signalling pathway in the liver of mice.

Conclusions
CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.
Symptomatic scrotal-inguino-retroperitoneal lymphocele in a kidney transplant patient—to drain but how to drain?
Authors: Ng Hung Shin Brian , Tan Samuel X , Griffin Anthony , Kanagarajah Vijay , Tan Ailin 
Published: April 2023

Abstract
Scrotal-inguino-retroperitoneal (SIR) lymphocele is a rare complication following kidney transplant. This entity is characterized by a tract originating in the retroperitoneal space, through the inguinal canal and scrotum following lymph hydrodissection. Systematic review investigating SIR lymphocele yielded cases with open fenestration of the sac into the peritoneum as treatment. We described a case report of a male in his 60s with a functioning kidney transplant and SIR lymphocele, which was successfully managed in the short term with percutaneous drainage of the collection. However, the collection recurred and computed tomography scan showed a multiloculated collection that prompted surgical management. Intraoperatively, the encapsulated fluid-filled tract was excised and a drain was placed, which was removed 48 h later. The patient wore a hernia belt for 6 weeks as support. He had no recurrence of his lymphocele following serial reviews for 9 months now.