bluuebunny/crossref_metadata_2025 huggingface dataset:
66 Relative efficacy of sacubitril/valsartan, dapagliflozin and vericiguat: a systematic review and network meta-analysis
Authors: Georgiopoulos Georgios , Aimo Alberto , Pateras Kostantinos , Stamatelopoulos Kimon , Lombardi Carlo Mario , Passino Claudio , Emdin Michele
Published: December 2020

Aims

Sacubitril/valsartan, dapagliflozin and vericiguat have shown a prognostic benefit in phase 3 trials on heart failure with reduced ejection fraction (HFrEF). Assessing their relative efficacy is an important goal.

Methods and results

We assessed the relative efficacy of dapagliflozin, sacubitril/valsartan and vericiguat, by comparing the treatment arms with the respective control arms (standard of care) through a network meta-analysis.

The phase 3 trials (PARADIGM-HF, DAPA-HF, VICTORIA), the HFrEF subgroup of DECLARE-TIMI 58, and a phase 2 trial on vericiguat were evaluated. Dapagliflozin was associated with a non-significant reduction in the risk of cardiovascular (CV) death or HF hospitalization compared to sacubitril/valsartan (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.64 to 1.22) and vericiguat (HR 0.82, 95% CI 0.6 to 1.12). The risk of CV death did not differ significantly between patients on dapagliflozin or sacubitril/valsartan (HR 0.90, 95% CI 0.51 to 1.58), and between patients on dapagliflozin or vericiguat (HR 0.77, 95% CI 0.44 to 1.37). As for HF hospitalization, dapagliflozin conferred a significant benefit over vericiguat (HR 0.77, 95% CI 0.63 to 0.93), but not over sacubitril/valsartan (HR 0.87, 95% CI 0.72 to 1.06). Dapagliflozin was ranked as the most effective therapy, followed by sacubitril/valsartan and vericiguat.

Conclusion

Based on an indirect comparison, dapagliflozin is not associated with a significantly lower risk of CV death or HF hospitalization or CV death alone compared to sacubitril/valsartan or vericiguat. The risk of HF hospitalization does not differ significantly between patients on dapagliflozin or sacubitril/valsartan, while dapagliflozin is superior to vericiguat.

Registration number

PROSPERO ID 186351.
506 Uneventful pseudoaneurysm of the ascending aorta with sternal erosion in pregnancy
Authors: Benedetti Alice , Del Monte Alvise , Rubino Maurizio , Mancuso Daniela
Published: December 2020

A 36-year-old woman at 31 weeks’ gestation presented with exertional dyspnoea and palpitations. She had a history of bicuspid aortic valve treated with surgical aortic valvotomy for severe stenosis, followed by ascending aorta replacement for type A acute aortic dissection and Bentall operation with a mechanical valve for severe aortic regurgitation. Eight years after the last surgery, magnetic resonance angiography showed aortic arch aneurysm (49 mm) with a small intimal flap. Thereafter, the patient was lost to follow-up until the current admission. She was hemodynamically stable on presentation and physical examination was unremarkable apart from a mechanical second heart sound. The electrocardiogram showed sinus rhythm with left bundle branch block (Panel A). Transthoracic echocardiography revealed severe left ventricular dilation (EDV 90 ml/m2) with mild dysfunction (EF 50%), normal prosthetic aortic valve function, and aortic arch dilation (50 mm) (Panel B and C). After a multidisciplinary evaluation, elective cesarean section was performed at 34 weeks’ gestation. A post-delivery aortic computed tomography angiography revealed aortic arch aneurysm (52 mm) with intimal flap and two pseudoaneurysms of the anterior aortic wall causing sternal erosion (Panel D, E, F and G). Subsequently, the patient underwent ascending aorta and aortic arch replacement by Frozen Elephant Trunk technique with a 24 x130 mm prosthesis between the aortic root and the descending aorta. The postoperative course was uneventful, and the patient was discharged to a cardiac rehabilitation centre.
Risk of ventricular arrhythmia in cardiac resynchronization therapy responders and super-responders: a systematic review and meta-analysis
Authors: Yuyun Matthew F , Erqou Sebhat A , Peralta Adelqui O , Hoffmeister Peter S , Yarmohammadi Hirad , Echouffo Tcheugui Justin B , Martin David T , Joseph Jacob , Singh Jagmeet P
Published: December 2020

Aims

Response to cardiac resynchronization therapy (CRT) is associated with improved survival, and reduction in heart failure hospitalization, and ventricular arrhythmia (VA) risk. However, the impact of CRT super-response [CRT-SR, increase in left ventricular ejection fraction (LVEF) to ≥ 50%] on VA remains unclear.

Methods and results

We undertook a meta-analysis aimed at determining the impact of CRT response and CRT-SR on risk of VA and all-cause mortality. Systematic search of PubMed, EMBASE, and Cochrane databases, identifying all relevant English articles published until 31 December 2019. A total of 34 studies (7605 patients for VA and 5874 patients for all-cause mortality) were retained for the meta-analysis. The pooled cumulative incidence of appropriate implantable cardioverter-defibrillator therapy for VA was significantly lower at 13.0% (4.5% per annum) in CRT-responders, vs. 29.0% (annualized rate of 10.0%) in CRT non-responders, relative risk (RR) 0.47 [95% confidence interval (CI) 0.39–0.56, P < 0.0001]; all-cause mortality 3.5% vs. 9.1% per annum, RR of 0.38 (95% CI 0.30–0.49, P < 0.0001). The pooled incidence of VA was significantly lower in CRT-SR compared with CRT non-super-responders (non-responders + responders) at 0.9% vs. 3.8% per annum, respectively, RR 0.22 (95% CI 0.12–0.40, P < 0.0001); as well as all-cause mortality at 2.0% vs. 4.3%, respectively, RR 0.47 (95% CI 0.33–0.66, P < 0.0001).

Conclusions

Cardiac resynchronization therapy super-responders have low absolute risk of VA and all-cause mortality. However, there remains a non-trivial residual absolute risk of these adverse outcomes in CRT responders. These findings suggest that among CRT responders, there may be a continued clinical benefit of defibrillators.
De Novo variants in EEF2 cause a neurodevelopmental disorder with benign external hydrocephalus
Authors: Nabais Sá Maria J , Olson Alexandra N , Yoon Grace , Nimmo Graeme A M , Gomez Christopher M , Willemsen Michèl A , Millan Francisca , Schneider Alexandra , Pfundt Rolph , de Brouwer Arjan P M , Dinman Jonathan D , de Vries Bert B A
Published: December 2020

Eukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder (NDD). Individuals shared a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly. Populational data and bioinformatic analysis underscored the pathogenicity of all de novo missense variants. The eEF2 yeast model strains demonstrated that patient-derived variants affect cellular growth, sensitivity to translation inhibitors and translational fidelity. Consequently, we propose that pathogenic variants in the EEF2 gene, so far exclusively associated with late-onset SCA26, can cause a broader spectrum of neurologic disorders, including childhood-onset NDDs and benign external hydrocephalus.
Disruption and recovery of testicular function during and after androgen abuse: the HAARLEM study
Authors: Smit D L , Buijs M M , de Hon O , den Heijer M , de Ronde W
Published: December 2020

STUDY QUESTION

What is the speed and extent by which endogenous testosterone production and spermatogenesis recover after androgen abuse?

SUMMARY ANSWER

Testosterone concentrations normalized within 3 months after discontinuation of androgen abuse in most subjects but recovery of spermatogenesis took longer—approximately 1 year.

WHAT IS KNOWN ALREADY

An estimated 4–6% of amateur strength athletes use androgens. Abuse of supraphysiological doses of androgens completely suppresses endogenous testosterone production and spermatogenesis.

STUDY DESIGN, SIZE, DURATION

Prospective and observational cohort study in which 100 male amateur athletes participated for 1 year.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Subjects (≥18 years) were included if they had not used androgens for at least 3 months and intended to start an androgen cycle within 2 weeks. Clinic visits took place before (T0), at the end (T1), and 3 months after the end of the cycle (T2), and 1 year after start of the cycle (T3), and included a blood test for gonadotrophins and sex hormones, and semen analysis.

MAIN RESULTS AND THE ROLE OF CHANCE

During androgen abuse, 77% of subjects had a total sperm count (TSC) below 40 million. Three months after the end of the cycle (T2), total (−1.9 nmol/l, CI −12.2 to 8.33, P = 0.71) and free (−38.6 pmol/l, CI −476 to 399, P = 0.86) testosterone concentrations were not different compared to baseline, whereas mean TSC was 61.7 million (CI 33.7 to 90.0; P < 0.01) lower than baseline. At the end of follow-up (T3), there was no statistically significant difference for total (−0.82 nmol/l, CI −11.5 to 9.86, P = 0.88) and free (−25.8 pmol/l, CI −480 to 428, P = 0.91) testosterone compared to baseline, but there was for TSC (−29.7 million, CI −59.1 to −0.39, P = 0.05). In nine (11%) subjects, however, testosterone concentrations were below normal at the end of follow-up (T3), and 25 (34%) subjects still had a TSC below 40 million.

LIMITATIONS, REASONS FOR CAUTION

The follow-up period (after the cycle) was relatively short, especially considering the long recovery time of spermatogenesis after discontinuation of androgens.

WIDER IMPLICATIONS OF THE FINDINGS

Endogenous testosterone production and spermatogenesis recover following androgen abuse in the vast majority of users. Nevertheless, not all users achieve a normalized testicular function. This may especially be the case for athletes with a high past exposure to androgens.

STUDY FUNDING/COMPETING INTEREST(S)

There is no conflict of interest. The study was funded by the Spaarne Gasthuis academy.

TRIAL REGISTRATION NUMBER

N/A.
Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease
Authors: Alkaissi Lina Y , Winberg Martin E , Heil Stéphanie D S , Haapaniemi Staffan , Myrelid Pär , Stange Eduard F , Söderholm Johan D , Keita Åsa V
Published: December 2020

Background

The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo.

Methods

An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA.

Results

There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls.

Conclusions

Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.
A systematic review on lagged associations in climate–health studies
Authors: Wang Pin , Zhang Xuyi , Hashizume Masahiro , Goggins William B , Luo Chao
Published: December 2020

Background

Lagged associations in climate–health studies have already been ubiquitously acknowledged in recent years. Despite extensive time-series models having proposed accounting for lags, few studies have addressed the question of maximum-lag specification, which could induce considerable deviations of effect estimates.

Methods

We searched the PubMed and Scopus electronic databases for existing climate–health literature in the English language with a time-series or case-crossover study design published during 2000–2019 to summarize the statistical methodologies and reported lags of associations between climate variables and 14 common causes of morbidity and mortality. We also aggregated the results of the included studies by country and climate zone.

Results

The associations between infectious-disease outcomes and temperatures were found to be lagged for ∼1–2 weeks for influenza, 3–6 weeks for diarrhoea, 7–12 weeks for malaria and 6–16 weeks for dengue fever. Meanwhile, the associations between both cardiovascular and respiratory diseases and hot temperatures lasted for <5 days, whereas the associations between cardiovascular diseases and cold temperatures were observed to be 10–20 days. In addition, rainfall showed a 4- to 10-week lagged association with infectious diarrheal diseases, whereas the association could be further delayed to 8–12 weeks for vector-borne diseases.

Conclusion

Our findings indicated some general patterns for possible lagged associations between some common health outcomes and climatic exposures, and suggested a necessity for a biologically plausible and reasonable definition of the effect lag in the modelling practices for future environmental epidemiological studies.
Regulating innovation in the early development of cell therapies
Authors: Exley Andrew R , McBlane James
Published: December 2020

Clinical need for paradigm shifts in efficacy and safety is driving the rapid and wide-ranging innovation in cell therapies for cancer beyond existing regulatory frameworks. Critical issues emerging during clinical trials frequently reflect unresolved elements of the regulation of innovation conundrum from earlier stages of development. We address this challenge using a global regulators’ perspective on the preclinical development of cell therapies, as a navigational aid to intended commercial use which maximises the clinical relevance of developmental data. We examine the implications of tumour targeting based on B cell, natural killer cell, conventional and unconventional T cell receptor domains; multiplex approaches; genetic manipulation strategies; and autologous versus allogeneic cell sources. We propose that detailed characterisation of both the cell source and final product is critical to optimising manufacture of individualised autologous or off the shelf allogeneic cell therapies, enabling product consistency to underpin extrapolation of clinical trial data to the expected commercial use. We highlight preclinical approaches to characterising target antigens including the Human Cell Atlas initiative, multi-dimensional cell culture, and safety testing against activated, proliferating or stressed control cells. Practical solutions are provided for preclinical toxicity studies when cell therapies target uniquely human tumour antigens, including illustrative mitigation measures for potential toxicity likely to support timely approval of first-in-human clinical trials. We recommend addressing the regulation of innovation conundrum through serial engagement between innovators and regulators early in the development of cell therapies for cancer, accelerating patient access while safeguarding against unacceptable toxicities.
A Pilot Study of Human Papillomavirus Detection in Urine Using a Novel Nucleic Acid Amplification Test
Authors: Marcus Jenna Z , Abedin Yasmin , Pierz Amanda J , Taveras Yanille , Sollecito Christopher C , Parmar Heta , Burk Robert D , Castle Philip E
Published: December 2020

Introduction

Human papillomavirus (HPV) testing is the standard-of-care for cervical cancer screening globally. Urine is a promising alternative to collecting a cervical specimen during a pelvic exam for HPV testing. There are no studies to date of HPV testing of urine using the Xpert HPV test.

Methods

We conducted a pilot study of 40 women; 30 women undergoing colposcopy because of a previous abnormality and 10 undergoing routine screening, to evaluate HPV detection in urine by the Xpert HPV test on the GeneXpert platform. Xpert HPV testing of urine was done according to the manufacturer’s instructions for testing cervical specimens. These results were compared to a reference of combined results of 2 research HPV genotyping tests conducted on cervical specimens and to repeat Xpert HPV testing of urine.

Results

Analytic sensitivity and specificity of Xpert testing of urine for any high-risk HPV versus the cervical sample, categorized as HPV positive if at least 1 test was positive, were 64.3% (95% confidence interval [95%CI]  = 42.1–76.1%) and 100% (97.5%CI = 71.5–100%), respectively. Analytic sensitivity and specificity of Xpert testing of urine for any high-risk HPV versus the cervical sample, categorized as positive if both tests were positive, were 66.7% (95%CI = 44.7–84.4%) and 86.7% (95%CI = 59.5–98.3%), respectively. Kappa values for first vs. second and first vs. third testing of urine by Xpert were 0.89 (95%CI = 0.79–1.00) and 0.90 (95%CI = 0.81–1.00), respectively.

Discussion

Given the call for global elimination of cervical cancer and widespread availability of GeneXpert, optimizing Xpert HPV testing of urine may be warranted.
Comparison of performance of F1 Romanov crossbred ewes with wool and hair breeds during fall lambing and body weight and longevity through six production years
Authors: Murphy Thomas W , Freking Brad A
Published: December 2020

The objective of this study was to evaluate wool (Dorset and Rambouillet) and hair (Dorper, Katahdin, and White Dorper) breeds for their ability to complement Romanov germplasm in an annual fall lambing system by estimating direct maternal grandsire and sire breed effects on economically important lamb and ewe traits. After 3 yr of evaluation under spring lambing, ewes of the five F1 types were transitioned to spring mating, exposed to composite terminal sires, and evaluated under a barn lambing system at 4, 5, and 6 yr of age. A total of 527 first generation crossbred (F1) ewes produced 1,151 litters and 2,248 lambs from 1,378 May exposures. After accounting for differences in dam age, birth type, and sex, lamb survival to weaning was unaffected by maternal grandsire breed (P = 0.30). However, lambs born to 50% Dorset (16.8 ± 0.21 kg) or 50% White Dorper ewes (16.8 ± 0.28 kg) were heavier at weaning than those born to 50% Katahdin dams (13.8 ± 0.32 kg; P < 0.001). Additionally, lambs born to 50% Dorset ewes were heavier than those born to 50% Rambouillet (16.0 ± 0.22 kg) and 50% Dorper ewes (15.7 ± 0.33; P ≤ 0.03), but no other pairwise maternal grandsire breed differences were observed (P ≥ 0.06). Ewe body weight (n = 3,629) was recorded prior to each of six possible mating seasons and, across ages, was greatest for Dorset- and Rambouillet-sired ewes (56.7 ± 0.44 and 56.5 ± 0.45 kg, respectively), intermediate for Dorper- and White Dorper-sired ewes (54.7 ± 0.78 and 54.1 ± 0.64 kg, respectively), and least for Katahdin-sired ewes (51.5 ± 0.45 kg). Fertility after spring mating (0.80 ± 0.03 to 0.87 ± 0.02), litter size at birth (1.46 ± 0.09 to 1.71 ± 0.07), and litter size at weaning (1.25 ± 0.06 to 1.46 ± 0.06) were not impacted by sire breed (P ≥ 0.16). Ewe longevity, assessed as the probability of being present after 6 production years, was also not affected by sire breed (0.39 ± 0.03 to 0.47 ± 0.03; P = 0.44). Rambouillet-sired ewes weaned more total weight of lamb (21.5 ± 0.94 kg) than Katahdin-sired ewes (17.8 ± 0.94 kg; P = 0.05), but no other sire breed differences were detected (P ≥ 0.07). Results demonstrated that incorporating the Romanov into a crossbreeding system is a practical means of improving out-of-season ewe productivity.
The effect of life history events on carcass merit and price of cull dairy cows
Authors: Moreira Ligia C , Passafaro Tiago L , Schaefer Daniel M , Rosa Guilherme J M
Published: December 2020

Cull dairy cows contribute almost 10% of national beef production in the United States. However, different factors throughout the life of dairy cows affect their weight and overall body condition as well as carcass traits, and consequently affect their market price. Therefore, the objectives of this study were: (1) to assess relationships between price ratio and carcass merit of cull dairy cows sold through several sites of an auction market and (2) to investigate the effect of animal life history events and live weight on sale barn price (BP) and price ratio (as a measure of relative price), as an indicator of carcass merit. Data from 4 dairy operations included 3,602 cull dairy cow records during the period of 2015 to 2019. Life history events data were collected from each dairy operation through Dairy Comp software; live weight and price were obtained periodically from the auction market, and the carcass data were provided by a local packing plant. Cow price in dollars per unit of live weight ($/cwt) and price ratio were the 2 outcome variables used in the analyses. Price ratio was created aiming to remove seasonality effects from BP (BP divided by the national average price for its respective month and year of sale). The association between price ratio and carcass merit traits was investigated using canonical correlation analysis, and the effect of life history events on both BP and price ratio was inferred using a multiple linear regression technique. More than 70% of the cows were culled in the first 3 lactations, with an average live weight of 701.5 kg, carcass weight of 325 kg, and dressing percentage of 46.3%. On average, cull cows were sold at $57.0/cwt during the period considered. The canonical correlation between price ratio and carcass merit traits was 0.76, indicating that price ratio reflected carcass merit of cull cows. Later lactations led to lower BP compared with cows culled during the first 2 lactations. Injury, and leg and feet problems negatively affected BP. Productive variables demonstrated that the greater milk production might lead to lower cow prices. A large variation between farms was also noted. In conclusion, price ratio was a good indicator of carcass merit of cull cows, and life history events significantly affected sale BP and carcass merit of cull cows sold through auction markets.
Adulticidal Efficacy and Sublethal Effects of Metofluthrin in Residual Insecticide Blends Against Wild Aedes albopictus (Diptera: Culicidae)
Authors: Bibbs Christopher S , Kaufman Phillip E , Xue Rui-De
Published: December 2020

Field development for optimizing the use patterns of spatial repellents are an ongoing research need. To investigate volatile pyrethroids in blends containing multiple active ingredients, metofluthrin was formulated into a vegetation spray for application to foliage and mosquito harborage. Metofluthrin was compared by itself and in combination with Sector (permethrin), Hyperion (sumithrin), Onslaught Fast Cap (s-fenvalerate, prallethrin), and against a benchmark for comparison, OneGuard (λ-cyhalothrin, prallethrin, pyriproxyfen). Field sites with established Aedes albopictus (Skuse) (Diptera: Culicidae) populations were allocated as control and treatment and surveilled with both adult traps and oviposition cups before and after treatment. Adult mosquito reductions were consistently higher over 4 wk in the combination treatments and were comparable to OneGuard. In contrast, efficacy provided by metofluthrin alone or the standalone existing product (Sector, Hyperion, Onslaught) by were consistently less effective than OneGuard and the comparative blends. Additionally, poorly melanized and collapsing eggs were identified from mosquito adults collected at treated field sites. A 20–50% significant decrease in nonviable mosquito eggs, a 50% or more reduction in total eggs and an 80% or more reduction in adult mosquitoes collected at the local field sites was demonstrated across all metofluthrin-containing treatments. Metofluthrin applications both supplemented the adulticidal control of the selected pyrethroid-containing products and provided significant reduction in egg laying frequency and viability during monitoring of areas adjacent to the treated vegetation. Metofluthrin, and possibly other volatile ingredients, appears to have complex interactions for mosquito control in the field and could be unique as a supporting ingredient to other insecticides.
Can Trade Taxes be a Major Source of Government Revenue?
Authors: Lashkaripour Ahmad
Published: December 2020

The tariff-for-revenue argument has been invoked repeatedly in recent years to justify protectionism. It is motivated by the belief that a country with market power can use trade taxes to raise revenue from foreign consumers and producers. This paper develops a new sufficient statistics methodology to evaluate this claim for a wide range of countries. I show that (a) even large countries have limited market power. (b) So, before retaliation by trading partners, the average country can beneficially replace only 16% of its domestic tax revenues with trade taxes. (c) After retaliation, however, 50% of the collected trade tax revenues disappear, governments are forced to increase domestic taxes to counter their shrinking tax base, and real gross domestic product drops across-the-board by an average of 7%. On the flip side, these findings indicate (d) the gains from multilateral trade agreements are also 30% larger once we account for the fiscal cost of trade wars.
Estimation of shallow subsurface S-wave velocity structure in urban area based on inversion of apparent dispersion curve
Authors: You Zhiwei , Xu Peifen , Ling Suqun , Du Yanan , Zhang Ruohan , Yao Jin , Zhang Hua
Published: December 2020

Due to its efficiency, convenience, non-destructive nature and strong anti-interference capability, the microtremor survey method (MSM) has found wide applications in urban geological surveys. The spatial autocorrelation method is diffusely applied to extract the dispersion curves from microtremor signals, which needs to satisfy the assumption that the energy of the fundamental Rayleigh wave is dominant. However, for layered media containing a layer with a significant low- or high-velocity contrast, this assumption is distinctly incorrect for certain frequency ranges. We present a processing methodology comprising the extraction and inversion of the apparent dispersion curves based on extended spatial autocorrelation method and fast simulated-annealing algorithm. We analyse synthetic microtremor signals for three selected geological models, and then compare the S-wave velocity structures estimated from their inversions with the actual models. Subsequently, a filed data example is given to detect the shallow stratigraphic structures in Guangzhou city, China, in which the new MSM was used. The estimated two-dimensional S-wave velocity model provided an accurate description of the thickness and depth of the strata in the study area, based on a priori information. Moreover, the S-wave velocity structures estimated from the MSM and the results from the drilling match very well, indicating that MSM is a reliable geophysical technique in urban geological surveys. Combined with available borehole information, MSM can be a very robust and effective method for detecting the shallow three-dimensional velocity structures in an urban area.
Henry Clay Frick and the Museum of Fine Arts, Boston: the blockbuster exhibition of 1910
Authors: Scott Nancy
Published: December 2020

November 1909 the Museum of Fine Arts in Boston inaugurated its second home, in a grand neoclassical-style building, and premiered innovative exhibition designs based on research in European museums. Henry Clay Frick soon displayed fifty of his paintings in the museum’s Old Masters gallery – the only occasion in his lifetime that he would lend such an expansive selection of paintings from his collection to a civic museum. Archival discoveries offer a reconstruction of the historic moment that brought together the new Boston museum, Frick’s paintings and an engaged public, shaping Frick’s vision of his collection’s legacy.
Examining the power of the social imaginary through competing narratives of data ownership in health research
Authors: Sorbie Annie , Gueddana Wifak , Laurie Graeme , Townend David
Published: December 2020

This article explores the social imaginary in the context of data ownership and the (non-)delivery of the data sharing revolution in biomedicine. We contribute to this special issue on imaginaries by developing a method and paradigm of ‘competing narratives’. Despite multiple initiatives to encourage health data sharing, and a strong ‘open access’ agenda, the data sharing revolution is not yet delivered. Ownership is persistently (though inconsistently) presented as a barrier to data sharing. However, existing literature does not reveal how far appeals to ownership are part of the problem. This paper reports original, interdisciplinary research asking: in health research, in what ways, if at all, do notions of ownership (broadly conceived) of health-related data impact on sharing practices? Doctrinal and empirical research methods are used to expose evidence of drivers behind appeals to ownership in health data sharing. The findings speak to how funders and data custodians can better tailor existing and potential data sharing initiatives to perspectives and behaviors. The concept of ‘my data’ is important: notions of reward, opportunity, control, and safeguarding establish legitimate, potentially competing ‘ownership’ interests in data. In particular, this research raises questions about the long-term effectiveness of an open access ideology that ignores these subtleties. In conclusion we find power in the social imaginary of ownership with respect to biomedical data; however, that power emerges and is enacted in unexpected ways by multiple actors within the ecosystem, often driven by competing narratives about what is at stake. Importantly, formal legal property-type appeals to ownership appear to have far less power in the narratives about data than the ethical and social concerns that underpin responsible biomedical research.
A Descriptive Catalogue of Eight Medieval Manuscripts from Wadham College, Oxford
Authors: Stone Zachary E
Published: December 2020

Ranging from an eleventh-century Gospel Book to a fifteenth-century copy of John Gower's Confessio Amantis, the medieval manuscripts of Wadham College merit more extensive consideration than they have hitherto received. This article seeks to enable and encourage the continued investigation of Wadham College's manuscript collection by providing preliminary descriptions for eight manuscripts lacking modern descriptions (MSS 1, 2, 5, 9, 11, 12, 13, and 10.19).
Bookbinding History and Sacred Cows
Authors: Pearson David
Published: December 2020

Book history has increasingly developed a cohesive view of the printing, selling, owning, reading and use of books, but bookbinding continues to struggle to find its place in the teaching and perception of the disciple. This is counter-intuitive, and a missed opportunity, in a world in which we talk so much about the book as a material object. This paper examines the reasons, and challenges many of the assumptions or beliefs that remain endemic in binding history. It offers examples of ways in which a different approach to binding studies is needed, while considering debates about the relative usefulness of methodologies based around decoration, or structure. It sets out a philosophy, or methodology, for the study of bindings in a book-historical context, with some basic questions which we should bring to any binding before us.
Discovered: Joseph Étienne de Surville's Preface to the Poésies de Clotilde de Surville
Authors: Cole William
Published: December 2020

Joseph Étienne, marquis de Surville (1755–1798) composed a wildly successful book of poems, first published in 1803, that he passed off as the work of his ancestor Clotilde de Surville (c. 1405-c. 1498). A newly-discovered copy of the first edition—presented by the author's widow to a family friend—contains Joseph Étienne's preface, transcribed and published here for the first time.
A review of recent research on antifungal agents against dermatophyte biofilms
Authors: Pereira Fillipe de Oliveira
Published: December 2020

Dermatophytoses are inflammatory cutaneous mycoses caused by dermatophyte fungi of the genera Trichophyton, Microsporum, and Epidermophyton that affect both immunocompetent and immunocompromised individuals. With therapeutic failure, dermatophytoses can become chronic and recurrent. This is partly due to their ability to develop biofilms, microbial communities involved in a polymeric matrix attached to biotic or abiotic surfaces, contributing to fungal resistance. This review presents evidence accumulated in recent years on antidermatophyte biofilm activity. The following databases were used: Web of Science, Medline/PubMed (via the National Library of Medicine), Embase, and Scopus. Original articles published between 2011 and 2020, emphasizing the antifungal activity of conventional and new drugs against dermatophyte biofilms were eligible. A total of 11 articles met the inclusion criteria and were reviewed – the studies used in vitro and ex vivo (fragments of nails and hair) experimental models. The articles focused on reports of antibiofilm activity for conventional antifungals, natural drugs, and new therapeutic tools. The strains reported on were T. mentagrophytes, T. rubrum, T. tonsurans, M. canis, and M. gypseum. Between the studies, the wide variability of experimental conditions in vitro and ex vivo was observed. The data suggest the need for methodological standardization (at some minimum). This review systematically presents current studies involving agents that present antibiofilm activity against dermatophytes; and an overview of the ideal in vitro and ex vivo experimental conditions to guarantee biofilm formation that may assist future research.

Lay abstract

This review presents the current studies on the antibiofilm activities of drugs against dermatophytes and ideal experimental conditions, which might guarantee in vitro and ex vivo biofilm formation. It can be useful to examine the efficacy of new antimicrobial drugs against dermatophytes.
Anomalous gas in ESO 149-G003: a MeerKAT-16 view
Authors: Józsa Gyula I G , Thorat Kshitij , Kamphuis Peter , Sebokolodi Lerato , Maina Eric K , Wang Jing , Pieterse Daniëlle L A , Groot Paul , Ramaila Athanaseus J T , Serra Paolo , Andati Lexy A L , de Blok W J G , Hugo Benjamin V , Kleiner Dane , Maccagni Filippo M , Makhathini Sphesihle , Molnár Dániel Cs , Ramatsoku Mpati , Smirnov Oleg M , Bloemen Steven , Paterson Kerry , Vreeswijk Paul , McBride Vanessa , Klein-Wolt Marc , Woudt Patrick , Körding Elmar , Le Poole Rudolf , Goedhart Sharmila , Passmoor Sean S , Serylak Maciej , Dettmar Ralf-Jürgen
Published: December 2020

ESO 149-G003 is a close-by, isolated dwarf irregular galaxy. Previous observations with the ATCA indicated the presence of anomalous neutral hydrogen ($\rm{H{\small I}}$) deviating from the kinematics of a regularly rotating disc. We conducted follow-up observations with the MeerKAT radio telescope during the 16-dish Early Science programme as well as with the MeerLICHT optical telescope. Our more sensitive radio observations confirm the presence of anomalous gas in ESO 149-G003, and further confirm the formerly tentative detection of an extraplanar $\rm{H{\small I}}$ component in the galaxy. Employing a simple tilted-ring model, in which the kinematics is determined with only four parameters but including morphological asymmetries, we reproduce the galaxy’s morphology, which shows a high degree of asymmetry. By comparing our model with the observed $\rm{H{\small I}}$, we find that in our model, we cannot account for a significant (but not dominant) fraction of the gas. From the differences between our model and the observed data cube, we estimate that at least 7–8 per cent of the $\rm{H{\small I}}$ in the galaxy exhibits anomalous kinematics, while we estimate a minimum mass fraction of less than 1 per cent for the morphologically confirmed extraplanar component. We investigate a number of global scaling relations and find that, besides being gas-dominated with a neutral gas-to-stellar mass ratio of 1.7, the galaxy does not show any obvious global peculiarities. Given its isolation, as confirmed by optical observations, we conclude that the galaxy is likely currently acquiring neutral gas. It is either re-accreting gas expelled from the galaxy or accreting pristine intergalactic material.
Shape, colour, and distance in weak gravitational flexion
Authors: Fabritius II Joseph M , Arena Evan J , Goldberg David M
Published: December 2020

Canonically, elliptical galaxies might be expected to have a perfect rotational symmetry, making them ideal targets for flexion studies – however, this assumption has not been tested. We have undertaken an analysis of low- and high-redshift galaxy catalogues of known morphological type with a new gravitational lensing code, Lenser. Using colour measurements in the u − r bands and fit Sérsic index values, objects with characteristics consistent with early-type galaxies are found to have a lower intrinsic scatter in flexion signal than late-type galaxies. We find this measured flexion noise can be reduced by more than a factor of two at both low and high redshift.
Rampant False Detection of Adaptive Phenotypic Optimization by ParTI-Based Pareto Front Inference
Authors: Sun Mengyi , Zhang Jianzhi
Published: December 2020

Organisms face tradeoffs in performing multiple tasks. Identifying the optimal phenotypes maximizing the organismal fitness (or Pareto front) and inferring the relevant tasks allow testing phenotypic adaptations and help delineate evolutionary constraints, tradeoffs, and critical fitness components, so are of broad interest. It has been proposed that Pareto fronts can be identified from high-dimensional phenotypic data, including molecular phenotypes such as gene expression levels, by fitting polytopes (lines, triangles, tetrahedrons, and so on), and a program named ParTI was recently introduced for this purpose. ParTI has identified Pareto fronts and inferred phenotypes best for individual tasks (or archetypes) from numerous data sets such as the beak morphologies of Darwin’s finches and mRNA concentrations in human tumors, implying evolutionary optimizations of the involved traits. Nevertheless, the reliabilities of these findings are unknown. Using real and simulated data that lack evolutionary optimization, we here report extremely high false-positive rates of ParTI. The errors arise from phylogenetic relationships or population structures of the organisms analyzed and the flexibility of data analysis in ParTI that is equivalent to p-hacking. Because these problems are virtually universal, our findings cast doubt on almost all ParTI-based results and suggest that reliably identifying Pareto fronts and archetypes from high-dimensional phenotypic data are currently generally difficult.
Endoplasmic reticulum stress: a key regulator of the follicular microenvironment in the ovary
Authors: Harada Miyuki , Takahashi Nozomi , Azhary Jerilee Mk , Kunitomi Chisato , Fujii Tomoyuki , Osuga Yutaka
Published: December 2020

Intra-ovarian local factors regulate the follicular microenvironment in coordination with gonadotrophins, thus playing a crucial role in ovarian physiology as well as pathological states such as polycystic ovary syndrome (PCOS). One recently recognized local factor is endoplasmic reticulum (ER) stress, which involves the accumulation of unfolded or misfolded proteins in the ER related to various physiological and pathological conditions that increase the demand for protein folding or attenuate the protein-folding capacity of the organelle. ER stress results in activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which affect a wide variety of cellular functions. Recent studies have revealed diverse roles of ER stress in physiological and pathological conditions in the ovary. In this review, we summarize the most current knowledge of the regulatory roles of ER stress in the ovary, in the context of reproduction. The physiological roles of ER stress and the UPR in the ovary remain largely undetermined. On the contrary, activation of ER stress is known to impair follicular and oocyte health in various pathological conditions; moreover, ER stress also contributes to the pathogenesis of several ovarian diseases, including PCOS. Finally, we discuss the potential of ER stress as a novel therapeutic target. Inhibition of ER stress or UPR activation, by treatment with existing chemical chaperones, lifestyle intervention, or the development of small molecules that target the UPR, represents a promising therapeutic strategy.
Shrinkage improves estimation of microbial associations under different normalization methods
Authors: Badri Michelle , Kurtz Zachary D , Bonneau Richard , Müller Christian L
Published: December 2020

Estimation of statistical associations in microbial genomic survey count data is fundamental to microbiome research. Experimental limitations, including count compositionality, low sample sizes and technical variability, obstruct standard application of association measures and require data normalization prior to statistical estimation. Here, we investigate the interplay between data normalization, microbial association estimation and available sample size by leveraging the large-scale American Gut Project (AGP) survey data. We analyze the statistical properties of two prominent linear association estimators, correlation and proportionality, under different sample scenarios and data normalization schemes, including RNA-seq analysis workflows and log-ratio transformations. We show that shrinkage estimation, a standard statistical regularization technique, can universally improve the quality of taxon–taxon association estimates for microbiome data. We find that large-scale association patterns in the AGP data can be grouped into five normalization-dependent classes. Using microbial association network construction and clustering as downstream data analysis examples, we show that variance-stabilizing and log-ratio approaches enable the most taxonomically and structurally coherent estimates. Taken together, the findings from our reproducible analysis workflow have important implications for microbiome studies in multiple stages of analysis, particularly when only small sample sizes are available.
Risk Factors, Screening, and Treatment Challenges in Staphylococcus aureus Native Septic Arthritis
Authors: Gobao Valerie C , Alfishawy Mostafa , Smith Clair , Byers Karin E , Yassin Mohamed , Urish Kenneth L , Shah Neel B
Published: December 2020

Background

Staphylococcus aureus is the most common cause of native septic arthritis. Few studies have characterized this disease during the US opioid epidemic. The role of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening in this disease has not been elucidated. We sought to identify risk factors and outcomes for S. aureus native septic arthritis and to evaluate MRSA screening in this disease.

Methods

A retrospective cohort study of native septic arthritis patients (2012–2016) was performed. Demographics, risk factors, and outcomes were compared between Staphylococcus aureus and other native septic arthritis infections. Sensitivity, specificity, and predictive values of MRSA screening were assessed.

Results

Two hundred fifteen cases of native septic arthritis were included. S. aureus was cultured in 64% (138/215). MRSA was cultured in 23% (50/215). S. aureus was associated with injection drug use (odds ratio [OR], 4.33; 95% CI, 1.74–10.81; P = .002) and switching antibiotics (OR, 3.92; 95% CI, 1.01–21.38; P = .032). For every 10-year increase in age, the odds of S. aureus decreased (OR, 0.72; 95% CI, 0.60–0.87; P = .001). For 1-unit increases in Charlson comorbidity index score, the odds of S. aureus decreased (OR, 0.82; 95% CI, 0.73–0.91; P = .0004). MRSA screening during admission demonstrated a sensitivity of 0.59, specificity of 0.96, positive predictive value of 0.85, and negative predictive value of 0.84 for MRSA native septic arthritis.

Conclusions

The opioid epidemic may be contributing to a demographic shift in native septic arthritis to younger, healthier individuals. S. aureus native septic arthritis has unique risks, including injection drug use. MRSA screening may be useful to rule in MRSA native septic arthritis.
Candida Infective Endocarditis: A Retrospective Study of Patient Characteristics and Risk Factors for Death in 703 United States Cases, 2015–2019
Authors: Huggins Jonathan P , Hohmann Samuel , David Michael Z
Published: December 2020

Background

Candida endocarditis is a rare, sometimes fatal complication of candidemia. Past investigations of this condition are limited by small sample sizes. We used the Vizient clinical database to report on characteristics of patients with Candida endocarditis and to examine risk factors for in-hospital mortality.

Methods

This was a multicenter, retrospective cohort study of 703 inpatients admitted to 179 US hospitals between October 2015 and April 2019. We reviewed demographic, diagnostic, medication administration, and procedural data from each patient’s initial encounter. Univariate and multivariate logistic regression analyses were used to identify predictors of in-hospital mortality.

Results

Of 703 patients, 114 (16.2%) died during the index encounter. One hundred fifty-eight (22.5%) underwent an intervention on a cardiac valve. On multivariate analysis, acute and subacute liver failure was the strongest predictor of death (odds ratio [OR], 9.2; 95% confidence interval [CI], 4.8 –17.7). Female sex (OR, 1.9; 95% CI, 1.2–3.0), transfer from an outside medical facility (OR, 1.8; 95% CI, 1.1–2.8), aortic valve pathology (OR, 2.7; 95% CI, 1.5–4.9), hemodialysis (OR, 2.1; 95% CI, 1.1–4.0), cerebrovascular disease (OR, 2.2; 95% CI, 1.2–3.8), neutropenia (OR, 2.5; 95% CI, 1.3–4.8), and alcohol abuse (OR, 2.9; 95% CI, 1.3–6.7) were also associated with death on adjusted analysis, whereas opiate abuse was associated with a lower odds of death (OR, 0.5; 95% CI, 0.2–0.9).

Conclusions

We found that the inpatient mortality rate was 16.2% among patients with Candida endocarditis. Acute and subacute liver failure was associated with a high risk of death, whereas opiate abuse was associated with a lower risk of death.
Pneumocystis and Severe Acute Respiratory Syndrome Coronavirus 2 Coinfection: A Case Report and Review of an Emerging Diagnostic Dilemma
Authors: Rubiano Carlos , Tompkins Kathleen , Sellers Subhashini A , Bramson Brian , Eron Joseph , Parr Jonathan B , Schranz Asher J
Published: December 2020

We present a case of a critically ill patient with coronavirus disease 2019 (COVID-19) found to have acquired immune deficiency syndrome and Pneumocystis jirovecii pneumonia (PCP). Coronavirus disease 2019 and PCP co-occurrence is increasingly reported and may complicate diagnostic and therapeutic strategies. Patients with severe COVID-19 should be screened for underlying immunocompromise and coinfections should be considered.
Chapter IX
Authors: Collins Wilkie
Published: December 2020

I had just given a porter the necessary directions for taking my portmanteau to Mr Keller’s house, when I heard a woman’s voice behind me asking the way to the Poste Restante*—or, in our roundabout English phrase, the office of letters...