bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing an International Registry for Uterus Transplantation (IRUTx): Promises and Challenges
Authors: Hammond-Browning Natasha , Williams Nicola Jane
Published: July 2020

Uterus Transplantation (UTx) is an experimental vascular composite allograft designed to provide women with absolute uterine factor infertility with the opportunity to gestate and give birth to their future offspring. The number of UTx procedures performed worldwide now stands at ≥70 and as the number of cases performed increases so too does the volume of potential data that may be gathered to inform the development, practice and regulation of UTx. Given the value of this data, and the challenges associated with keeping track of cases and outcomes where data remains unpublished and/or scattered, scientists and academics conducting research into UTx have increasingly called for the swift creation, implementation and management of an international registry for Uterus Transplantation (IRUTx). This article explores and provides practical guidance regarding the potential benefits the IRUTx may provide to stakeholders, as well as the legal and ethical challenges that its creation may pose in terms of dataset design, consent, privacy, researcher compliance and governance.
Elevated levels of nitrous dioxide are associated with lower AMH levels: a real-world analysis
Authors: La Marca Antonio , Spaggiari Giorgia , Domenici Daniela , Grassi Roberto , Casonati Andrea , Baraldi Enrica , Trenti Tommaso , Simoni Manuela , Santi Daniele
Published: July 2020

STUDY QUESTION

Are there any associations between environmental pollutants and ovarian reserve, expressed by anti-Mullerian hormone (AMH) serum levels?

SUMMARY ANSWER

In this first real-world approach to demonstrate the relationship between air pollutants and serum AMH levels, adverse associations were observed for nitrogen dioxide (NO2) but not with particulate matter.

WHAT IS KNOWN ALREADY

In recent years, air pollution has emerged as a potential disrupter to the homeostasis of physiological hormones, possibly affecting human reproduction. Although the influence of age and smoking on AMH levels is largely accepted, the relationship between AMH and the environment has not currently been established.

STUDY DESIGN, SIZE, DURATION

A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed in a single laboratory from January 2007 to October 2017.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Serum AMH data were connected to patients’ age and residential address, to include air pollution data after geo-localisation. The air pollution considered daily particulate matter (PM) and NO2 values.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 1463 AMH measurements were collected (mean 1.94 ng/ml, median 0.90 ng/ml). AMH was inversely related to patients’ age in women older than 25 years (adjusted R-squared 0.120, P < 0.001), but not in those younger than 25 years (adjusted R-squared 0.068, P = 0.055). AMH levels were inversely related to environmental pollutants, such as PM10 (Rho = −0.088, P = 0.001), PM2.5 (Rho = −0.062, P = 0.021) and NO2 (Rho = −0.111, P < 0.001). After subdividing the dataset into quartiles for PM10 and PM2.5, the influence of age on AMH serum levels was found to be a stronger influence than that exerted by PM (P = 0.833 and P = 0.370, respectively). On the contrary, considering NO2 quartiles, higher AMH levels were observed in third quartile compared to fourth quartile, even after adjustment for age (P = 0.028), indicating a stronger influence of NO2 exposure on AMH serum levels. Considering an AMH cut-off of 0.3 ng/ml, a significant higher frequency of women with severe ovarian reserve reduction in the fourth quartile was shown only for NO2 (P = 0.010).

LIMITATIONS, REASONS FOR CAUTION

Several limitations should be underlined, such as the lack of information about work and life habits of each patient and the retrospective nature of the analysis performed on real-world data.

WIDER IMPLICATIONS OF THE FINDINGS

Although the genetic component is highly predictive for defining the ovarian reserve at birth, potentially modifiable environmental factors could influence the rate of decline in AMH and ovarian reserve during adulthood.

STUDY FUNDINGCOMPETING INTEREST(S)

Authors have neither funding nor competing interests to declare.

TRIAL REGISTRATION NUMBER

N/A.
Tracking the spatiotemporal variability of the oxic–anoxic interface in the Baltic Sea with broadband acoustics
Authors: Weidner Elizabeth , Stranne Christian , Sundberg Jonas Hentati , Weber Thomas C , Mayer Larry , Jakobsson Martin
Published: July 2020

Anoxic zones, regions of the water column completely devoid of dissolved oxygen, occur in open oceans and coastal zones worldwide. The Baltic Sea is characterized by strong salinity-driven stratification, maintained by occasional water inflows from the Danish Straights and freshwater input from rivers. Between inflow events, the stratification interface between surface and deep waters hinders mixing and ventilation of deep water; consequently, the bottom waters of large regions of the Baltic are anoxic. The onset of the anoxic zone is closely coincident with the depth of the halocline and, as a result, the interface between oxic and anoxic waters corresponds to a strong impedance contrast. Here, we track acoustic scattering from the impedance contrast utilizing a broadband split-beam echosounder in the Western Gotland Basin and link it to a dissolved oxygen level of 2 ml/l using ground truth stations. The broadband acoustic dataset provides the means to remotely observe the spatiotemporal variations in the oxic–anoxic interface, map out the extent of the anoxic zone with high resolution, and identify several mechanisms influencing the vertical distribution of oxygen in the water column. The method described here can be used to study other systems with applications in ongoing oceanographic monitoring programs.
Sympathetic innervation of canine pulmonary artery and morphometric and functional analysis in dehydromonocrotaline-induced models after pulmonary artery denervation
Authors: Jiang Xiaomin , Zhang Juan , Zhou Ling , Luo Jie , Wang Jinsong , Li Li , Chen Shaoliang
Published: July 2020

OBJECTIVES

We aimed to describe the anatomic distribution of periarterial pulmonary sympathetic nerves and to observe the long-term morphometric and functional changes after pulmonary artery denervation (PADN), a novel therapy for pulmonary arterial hypertension (PAH).

METHODS

A total of 45 beagles were divided into a sympathetic innervation group (n = 3, 33.3% were females), a PAH group (n = 35, 34.3% were females) and a control group (n = 7, 28.5% were females). The PAH group was randomly divided into no-PADN (n = 7), instant-PADN (n = 7), 1M-PADN (n = 7), 2M-PADN (n = 7) and 3M-PADN (n = 7) subgroups. The sympathetic innervation group was sacrificed to reveal the sympathetic innervation of pulmonary arteries. PAH was induced by injecting dehydromonocrotaline (DHMCT) through the right atrium. The pulmonary capillary wedge pressure, right ventricular systolic pressure, right ventricular mean pressure, pulmonary artery systolic pressure and pulmonary artery mean pressure of each group were continuously measured. The cardiac output was detected to calculate the pulmonary vascular resistance. PAH and control groups were subjected to immunofluorescence assay, sympathetic nerve conduction velocity measurement and transmission electron microscopy.

RESULTS

The no-PADN group had significantly higher PVSP, PVMP, pulmonary artery systolic pressure, pulmonary artery mean pressure and pulmonary vascular resistance but lower cardiac output than those of the control group (P < 0.05). Instant-PADN, 1M-PADN, 2M-PADN and 3M-PADN groups had significantly lower PVSP, PVMP, pulmonary artery systolic pressure, pulmonary artery mean pressure and pulmonary vascular resistance but higher cardiac output than those of the no-PADN group (P < 0.05). Most sympathetic nerves were located within 2.5 mm of the intimae of the bifurcation and proximal trunk, mainly in the left trunk. The diameter and cross-sectional area of myelinated fibres in the PAH group were significantly larger than those of the control group. Sympathetic nerve conduction velocity of the PAH group gradually decreased, and nerve fibres were almost demyelinated 3 months after PADN.

CONCLUSIONS

PADN effectively relieved dehydromonocrotaline-induced canine PAH and decreased sympathetic nerve conduction velocity.
Fundamental Inequality for Hyperbolic Coxeter and Fuchsian Groups Equipped with Geometric Distances
Authors: Kosenko Petr
Published: July 2020

We prove that the hitting measure is not equivalent to the Lebesgue measure for a large class of nearest-neighbour random walks on hyperbolic reflection groups and Fuchsian groups with regular Dirichlet polygons.
Immunoserologic Detection and Diagnostic Relevance of Cross-Reactive Autoantibodies in Coronavirus Disease 2019 Patients
Authors: Schiaffino María Teresa , Di Natale Marisa , García-Martínez Elena , Navarro Joaquín , Muñoz-Blanco José Luis , Demelo-Rodríguez Pablo , Sánchez-Mateos Paloma
Published: July 2020

Background

During the coronavirus disease 2019 (COVID-19) pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients.

Methods

The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections.

Results

We describe 12 patients positive for the cross-reactive antibody, compared with a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion.

Conclusions

Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for autoreactive-mediated complications such as thrombotic or neurologic events.
Prospective Study Comparing Deep Throat Saliva With Other Respiratory Tract Specimens in the Diagnosis of Novel Coronavirus Disease 2019
Authors: Lai Christopher K C , Chen Zigui , Lui Grace , Ling Lowell , Li Timothy , Wong Martin C S , Ng Rita W Y , Tso Eugene Y K , Ho Tracy , Fung Kitty S C , Ng Siu T , Wong Barry K C , Boon Siaw S , Hui David S C , Chan Paul K S
Published: July 2020

Background

Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain.

Methods

We performed a prospective study in 2 regional hospitals in Hong Kong.

Results

We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62–0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum.

Conclusions

Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.
Establishing Novel Molecular Algorithms to Predict Decreased Susceptibility to Ceftriaxone in Neisseria gonorrhoeae Strains
Authors: Lin Eric Y , Adamson Paul C , Deng Xiaomeng , Klausner Jeffrey D
Published: July 2020

Background

Globally, decreased susceptibility to ceftriaxone in Neisseria gonorrhoeae is rising. We aimed to compile a global collection of N. gonorrhoeae strains and assess the genetic characteristics associated with decreased susceptibility to ceftriaxone.

Methods

We performed a literature review of all published reports of N. gonorrhoeae strains with decreased susceptibility to ceftriaxone (>0.064 mg/L minimum inhibitory concentration) through October 2019. Genetic mutations in N. gonorrhoeae genes (penA, penB, mtrR, and ponA), including determination of penA mosaicism, were compiled and evaluated for predicting decreased susceptibility to ceftriaxone.

Results

There were 3821 N. gonorrhoeae strains identified from 23 countries and 684 (18%) had decreased susceptibility to ceftriaxone. High sensitivities or specificities (>95%) were found for specific genetic mutations in penA, penB, mtrR, and ponA, both with and without determination of penA mosaicism. Four algorithms to predict ceftriaxone susceptibility were proposed based on penA mosaicism determination and penA or non-penA genetic mutations, with sensitivity and specificity combinations up to 95% and 62%, respectively.

Conclusion

Molecular algorithms based on genetic mutations were proposed to predict decreased susceptibility to ceftriaxone in N. gonorrhoeae. Those algorithms can serve as a foundation for the development of future assays predicting ceftriaxone decreased susceptibility within N. gonorrhoeae globally.
Outcome of community-onset ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and urinary tract infection: a population-based cohort study in Denmark
Authors: Richelsen Rasmus , Smit Jesper , Schønheyder Henrik Carl , Laxsen Anru Pavithra , Gutiérrez-Gutiérrez Belen , Rodríguez-Bãno Jesús , Nielsen Henrik
Published: July 2020

Objectives

To assess the impact of ESBL production on mortality and length of hospital stay (LOS) of community-onset infections due to Escherichia coli or Klebsiella pneumoniae.

Methods

A population-based cohort study including all adult patients hospitalized with a first-time community-onset E. coli or K. pneumoniae bacteraemia or urinary tract infection in the North Denmark Region between 2007 and 2017. For each bacterial agent, we computed 1 year Kaplan–Meier survival curves and cumulative incidence functions of LOS, and by use of Cox proportional hazard regression we computed HRs as estimates of 30 day and 1 year mortality rate ratios (MRRs) and LOS among patients with and without ESBL-producing infections.

Results

We included 24 518 cases (among 22350 unique patients), of whom 1018 (4.2%) were infected by an ESBL-producing bacterium. The 30 day cumulative mortality and adjusted MRR (aMRR) in patients with and without ESBL-producing isolates was as follows: E. coli bacteraemia (n = 3831), 15.8% versus 14.0%, aMRR = 1.01 (95% CI = 0.70–1.45); E. coli urinary tract infection (n = 17151), 9.5% versus 8.7%, aMRR = 0.97 (95% CI = 0.75–1.26); K. pneumoniae bacteraemia (n = 734), 0% versus 17.2%, aMRR = not applicable; and K. pneumoniae urinary tract infection (n = 2802), 13.8% versus 10.7%, aMRR = 1.13 (95% CI = 0.73–1.75). The 1 year aMRR remained roughly unchanged. ESBL-producing E. coli bacteraemia was associated with an increased LOS compared with non-ESBL production.

Conclusions

ESBL production was not associated with an increased short- or long-term mortality in community-onset infections due to E. coli or K. pneumoniae, yet ESBL-producing E. coli bacteraemia was associated with an increased LOS.
Information needs and priority use cases of population health researchers to improve preparedness for future hurricanes and floods
Authors: Phuong Jimmy , Bandaragoda Christina J , Haldar Shefali , Stephens Kari A , Ordonez Patricia , Mooney Sean D , Hartzler Andrea L
Published: July 2020

Objective

Information gaps that accompany hurricanes and floods limit researchers’ ability to determine the impact of disasters on population health. Defining key use cases for sharing complex disaster data with research communities and facilitators, and barriers to doing so are key to promoting population health research for disaster recovery.

Materials and Methods

We conducted a mixed-methods needs assessment with 15 population health researchers using interviews and card sorting. Interviews examined researchers’ information needs by soliciting barriers and facilitators in the context of their expertise and research practices. Card sorting ranked priority use cases for disaster preparedness.

Results

Seven barriers and 6 facilitators emerged from interviews. Barriers to collaborative research included process limitations, collaboration dynamics, and perception of research importance. Barriers to data and technology adoption included data gaps, limitations in information quality, transparency issues, and difficulty to learn. Facilitators to collaborative research included collaborative engagement and human resource processes. Facilitators to data and technology adoption included situation awareness, data quality considerations, adopting community standards, and attractive to learn. Card sorting prioritized 15 use cases and identified 30 additional information needs for population health research in disaster preparedness.

Conclusions

Population health researchers experience barriers to collaboration and adoption of data and technology that contribute to information gaps and limit disaster preparedness. The priority use cases we identified can help address information gaps by informing the design of supportive research tools and practices for disaster preparedness. Supportive tools should include information on data collection practices, quality assurance, and education resources usable during failures in electric or telecommunications systems.
Beef trait genetic parameters based on old and recent data and its implications for genomic predictions in Italian Simmental cattle
Authors: Cesarani Alberto , Hidalgo Jorge , Garcia Andre , Degano Lorenzo , Vicario Daniele , Masuda Yutaka , Misztal Ignacy , Lourenco Daniela
Published: July 2020

This study aimed to evaluate the changes in variance components over time to identify a subset of data from the Italian Simmental (IS) population that would yield the most appropriate estimates of genetic parameters and breeding values for beef traits to select young bulls. Data from bulls raised between 1986 and 2017 were used to estimate genetic parameters and breeding values for four beef traits (average daily gain [ADG], body size [BS], muscularity [MUS], and feet and legs [FL]). The phenotypic mean increased during the years of the study for ADG, but it decreased for BS, MUS, and FL. The complete dataset (ALL) was divided into four generational subsets (Gen1, Gen2, Gen3, and Gen4). Additionally, ALL was divided into two larger subsets: the first one (OLD) combined data from Gen1 and Gen2 to represent the starting population, and the second one (CUR) combined data from Gen3 and Gen4 to represent a subpopulation with stronger ties to the current population. Genetic parameters were estimated with a four-trait genomic animal model using a single-step genomic average information restricted maximum likelihood algorithm. Heritability estimates from ALL were 0.26 ± 0.03 for ADG, 0.33 ± 0.04 for BS, 0.55 ± 0.03 for MUS, and 0.23 ± 0.03 for FL. Higher heritability estimates were obtained with OLD and ALL than with CUR. Considerable changes in heritability existed between Gen1 and Gen4 due to fluctuations in both additive genetic and residual variances. Genetic correlations also changed over time, with some values moving from positive to negative or even to zero. Genetic correlations from OLD were stronger than those from CUR. Changes in genetic parameters over time indicated that they should be updated regularly to avoid biases in genomic estimated breeding values (GEBV) and low selection accuracies. GEBV estimated using CUR variance components were less biased and more consistent than those estimated with OLD and ALL variance components. Validation results indicated that data from recent generations produced genetic parameters that more appropriately represent the structure of the current population, yielding accurate GEBV to select young animals and increasing the likelihood of higher genetic gains.
Death from Poppy Tea Consumption
Authors: Bishop-Freeman Sandra C , Fox Lauren , Winecker Ruth E , Hudson Jason S
Published: July 2020

The historical practice of brewing poppy tea for its opioid-like effects is reoccurring with modern-day substance users. We present four postmortem cases with toxicology results that serve as case studies for the potential hazards of poppy tea ingestion. There is limited information regarding the risks of this practice due to the variability of the morphine content of the opium exuded from the plant. While internet tea recipes offer guidance, differences in poppy cultivation, washing, and infusing time are some of the reasons why the beverage may contain inconsistent and clinically significant alkaloid concentrations for each preparation. Variability in opioid tolerance along with additional drugs taken will impact the overall degree of toxicity experienced from the opiates in the tea. Advancements in the genetic modification of the poppy plant could greatly alter the ratio of alkaloids seen in biological fluids and will be highly dependent on the source of the poppy product. The blood concentrations of free morphine and free codeine in cases 1–3 where the toxicity from the tea was considered the primary cause of death were 0.94 and 0.11 mg/L, 0.62 and 0.034 mg/L, and 0.16 and 0.010 mg/L, respectively. The urine concentrations of morphine and codeine were 13 and 0.94 mg/L in case 1 and 16 and 1.6 mg/L in case 2, respectively. The opium alkaloids thebaine and laudanosine were identified qualitatively by our routine organic base/neutral drug detection procedure.
Methyl-4-Hydroxybutyrate and Ethyl-4-Hydroxybutyrate as Potential Markers for Simultaneous Consumption of GHB/GBL and Alcohol: Preliminary Investigations
Authors: Küting Theresa , Beier Niklas , Krämer Michael , Madea Burkhard
Published: July 2020

γ-Hydroxybutyric acid (GHB) and its corresponding lactone γ-butyrolactone (GBL) are misused as knock out (k.o.) drugs. The short detection window and the major inter- and intra-individual variations of endogenous GHB concentrations in commonly used matrices such as blood and urine complicate the analytical proof of an exogenous GHB/GBL administration. We searched for an alternative way to prove an exogenous GHB/GBL administration via detection of methyl- and ethyl-4-hydroxybutyrate, which could arise in alcoholic solutions after spiking with GHB/GBL. A liquid chromatographic–triple quadrupole mass spectrometric method was developed and validated to quantitatively determine methyl- and ethyl-4-hydroxybutyrate in alcoholic beverages (limit of detection [LoD]: 5.8 and 3.4 ng/mL, respectively). A sample collective of alcoholic beverages (n = 47) revealed natural occurring amounts of ethyl-4-hydroxybutyrate (<LoD—approx. 3980 ng/mL) with higher concentrations particularly found in wine samples. Nearly no ethyl-4-hydroxybutyrate was observable in spirits/liqueurs and no methyl-4-hydroxybutyrate was detectable at all. A moderate correlation was shown between the ethyl-4-hydroxybutyrate concentration and the pH-value in wine samples (pH 2.9–3.7, n = 29) as well as between the ethyl-4-hydroxybutyrate concentration and the GHB concentration in all measured beverages (GHB:  <  limit of quantification [LoQ]—11.4 µg/mL, n = 47). A dependency on alcohol content could not be observed. A voluntary intake (n = 1) of 750-mL wine naturally containing high amounts of ethyl-4-hydroxybutyrate (approx. 2010 ng/mL) revealed no observable GHB-ester concentrations in blood and urine. Furthermore, an experiment simulating a beverage that could potentially be used in a drug-facilitated crime (DFC) case showed ethyl-4-hydroxybutyrate concentrations exceeding the concentrations naturally observed in beverage samples. However, in order to evaluate whether ethyl-4-hydroxybutyrate could be useful as marker for the co-consumption of GHB/GBL and alcohol and to prolong the detection window of unintended GHB/GBL intake, further experiments have to be performed.
Analysis of the Efficacy of Iloprost Treatment in Amputations Due to Burn
Authors: Sevil Fehim Can , Sevil Hülya , Tort Mehmet , Öztürk Mehmet
Published: July 2020

The aim of our study was to demonstrate the decrease in amputation rates with iloprost treatment in patients who develop vascular injury due to burns. The data of 366 adult burn patients who were admitted to the emergency department of our hospital between 2016 and 2019 were analyzed. Demographic characteristics, burn factors, vascular examination findings, medical treatments, amputation rates, and levels were recorded. The amputation rates of the patients who were treated with iloprost and who were not treated with iloprost were compared. The mean age of 366 adult patients treated for burns was 37.8 ± 16.4 years, and of these patients, 220 (59.9%) were under 40 years of age. Although heat burns (n = 331.85%) were the most common burn etiology, it was found that the incidence of vascular injury was higher in burns caused by electricity (11.7%) and cold (3.3%) (P < 0.001). Vascular injury was detected in 60 (16.3%) of the patients and 21 (35%) of these patients were treated with iloprost. Amputation was observed in 20 (5.5%) of all burn patients, but only one of the patients treated with iloprost underwent amputation (P < .001). The individual and social impacts of amputations caused by burns are unquestionable. The authors are of the opinion that iloprost treatment is effective in reducing amputations due to burns.
Phase 1b study to investigate the safety and tolerability of idelalisib in Japanese patients with relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia
Authors: Fukuhara Noriko , Kinoshita Tomohiro , Yamamoto Kazuhito , Nagai Hirokazu , Izutsu Koji , Yamamoto Go , Bhargava Pankaj , Rajakumaraswamy Nishan , Humeniuk Rita , Mathias Anita , Xing Guan , Fukui Masato , Tobinai Kensei
Published: July 2020

Objective

Idelalisib is an orally administered, highly selective inhibitor of phosphatidylinositol 3-kinase-δ. In this phase 1b study, the safety, tolerability and pharmacokinetics of idelalisib, an oral inhibitor of phosphatidylinositol 3-kinase-δ, were evaluated in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma.

Methods

In total, six patients (follicular lymphoma: n = 3, chronic lymphocytic leukemia: n = 3) were enrolled to receive idelalisib 150 mg twice daily.

Results

No dose-limiting toxicities were reported. The most common adverse events were diarrhea (n = 5), gastritis (n = 3), insomnia (n = 3) and pyrexia (n = 3). The most common ≥grade 3 adverse events were diarrhea (n = 2), increased transaminase levels (n = 2) and decreased appetite (n = 2). The maximum idelalisib plasma concentrations (Cmax) were achieved at 2.50 h (range: 1.50–4.00 h). The mean idelalisib plasma concentrations decreased over time but remained detectable in most patients at 12 h. All enrolled patients underwent efficacy evaluation by investigators, and five patients (follicular lymphoma: n = 2, chronic lymphocytic leukemia: n = 3) achieved partial response. The median duration of partial response was 14.5 months (range: 3.7–31.3 months).

Conclusion

Idelalisib 150 mg twice daily was considered tolerable in Japanese patients with follicular lymphoma or chronic lymphocytic leukemia.

(Clinical trial registration: NCT02242045)
Circadian activity patterns of mammalian predators and prey in Costa Rica
Authors: Botts Ryan T , Eppert Amy A , Wiegman Timothy J , Rodriguez Abner , Blankenship Steven R , Asselin Ellen M , Garley Wyatt M , Wagner Abigail P , Ullrich Sierra E , Allen Gabrielle R , Mooring Michael S
Published: July 2020

Temporal niche shifts can shape predator–prey interactions by enabling predator avoidance, enhancing feeding success, and reducing competition among predators. Using a community-based conservation approach, we investigated temporal niche partitioning of mammalian predators and prey across 12 long-term camera trap surveys in the Pacific slope and Talamanca Cordillera of Costa Rica. Temporal overlap and segregation were investigated between predator–prey and predator–predator pairs using overlap analysis, circular statistics, and relative abundance after accounting for differences in habitat, season, and human impact among sites. We made the assumption that predators select abundant prey and adjust their activity to maximize their temporal overlap, thus we predicted that abundant prey with high overlap would be preferred prey species for that predator. We also predicted that similar-sized pairs of predator species with the greatest potential for competitive interactions would have the highest temporal segregation. Our results supported the existence of temporal niche separation among the eight species of predators—the smaller Leopardus felids (ocelot, margay, oncilla) were primarily nocturnal, the largest felids (jaguar and puma) and coyote were cathemeral, and the smaller jaguarundi and tayra were mostly diurnal. Most prey species (67%) were primarily nocturnal versus diurnal or cathemeral (33%). Hierarchical clustering identified relationships among species with the most similar activity patterns. We discuss the primary prey and competitor species predicted for each of the eight predators. Contrary to our prediction, the activity pattern of similar-sized intraguild competitors overlapped more than dissimilar-sized competitors, suggesting that similar-sized predators are hunting the same prey at the same time. From this we conclude that prey availability is more important than competition in determining circadian activity patterns of Neotropical predators. Our results indicate the presence of a delicate balance of tropical food webs that may be disrupted by overhunting, leading to a depauperate community consisting of ubiquitous generalists and endangered specialists. With Central America a hotspot for hunting-induced “empty forests,” community-based conservation approaches may offer the best road to reduce illegal hunting and maintain the biodiversity and community structure of tropical forest systems.
Unusual presentation of small bowel GIST: diffuse omental & mesenteric sarcomatosis
Authors: Catarci Marco , Balla Andrea , Coppola Luigi
Published: July 2020

Gastrointestinal stromal tumors (GISTs) represent ~1% of gastrointestinal (GI) tract neoplasms. Unusual presentation of a small bowel GIST with diffuse omental and mesenteric implants in a symptomatic patient is reported. CT scan in a 68-years-old woman showed multiple processes with solid density and colliquation areas in the abdominal cavity. At surgery, an uncommon finding of multiple omental and mesenteric secondary implants was evident. The index mass with 40 cm of adjacent small bowel, omentum and all peritoneal lesions were completely removed. Definitive pathology report showed a small bowel GIST with focal areas of necrosis and high mitotic activity (35 mitosis/50 High Power Fields), with multiple metastases on mesentery and omentum. Patient was therefore submitted to adjuvant treatment with Imatinib and a close follow-up program. Small bowel GIST with high mitotic activity may present with diffuse omental and mesenteric peritoneal seedings. Complete surgical clearance remains the mainstay of treatment.
Laboratory quantification of a plenoptic wavefront sensor with extended objects
Authors: Zhang Zhentao , Bharmal Nazim , Morris Tim , Liang Yonghui
Published: July 2020

Adaptive optics (AO) is widely used in ground-based telescopes to compensate the effects of atmosphere distortion, and the wavefront sensor is a significant component in the AO systems. The plenoptic wavefront sensor has been proposed as an alternative wavefront sensor adequate for extended objects and wide field of views. In this paper, a experimental bench has been set up to investigate the slope measurement accuracy and closed-loop wavefront correction performance for extended objects. From the experimental results, it has been confirmed that plenoptic wavefront sensor is suitable for extended objects wavefront sensing with proper optical design. The slope measurements have a good linearity and accuracy when observing extended objects. The image quality is significantly improved after closed-loop correction. A method of global tip/tilt measurement using only plenoptic wavefront sensor frame is proposed in this paper, it is also a potential advantage of plenoptic wavefront sensor in extended objects wavefront sensing.
The cooling-down central star of the planetary nebula SwSt 1: a late thermal pulse in a massive post-AGB star?
Authors: Hajduk Marcin , Todt Helge , Hamann Wolf-Rainer , Borek Karolina , van Hoof Peter A M , Zijlstra Albert A
Published: July 2020

SwSt 1 (PN G001.5-06.7) is a bright and compact planetary nebula containing a late [WC]-type central star. Previous studies suggested that the nebular and stellar lines are slowly changing with time. We studied new and archival optical and ultraviolet spectra of the object. The [O iii] 4959 and 5007 Å to H β line flux ratios decreased between about 1976 and 1997/2015. The stellar spectrum also shows changes between these epochs. We modelled the stellar and nebular spectra observed at different epochs. The analyses indicate a drop of the stellar temperature from about 42 kK to 40.5 kK between 1976 and 1993. We do not detect significant changes between 1993 and 2015. The observations show that the star performed a loop in the H–R diagram. This is possible when a shell source is activated during its post-AGB evolution. We infer that a late thermal pulse (LTP) experienced by a massive post-AGB star can explain the evolution of the central star. Such a star does not expand significantly as the result of the LTP and does not became a born-again red giant. However, the released energy can remove the tiny H envelope of the star.
Extinction in the 11.2 µm PAH band and the low L11.2/LIR in ULIRGs
Authors: Hernán-Caballero Antonio , Spoon Henrik W W , Alonso-Herrero Almudena , Hatziminaoglou Evanthia , Magdis Georgios E , Pérez-González Pablo G , Pereira-Santaella Miguel , Arribas Santiago , Cortzen Isabella , Labiano Álvaro , Piqueras Javier , Rigopoulou Dimitra
Published: July 2020

We present a method for recovering the intrinsic (extinction-corrected) luminosity of the 11.2 μm PAH band in galaxy spectra. Using 105 high S/N Spitzer/IRS spectra of star-forming galaxies, we show that the equivalent width ratio of the 12.7 and 11.2 μm PAH bands is independent on the optical depth (τ), with small dispersion (∼5 per cent) indicative of a nearly constant intrinsic flux ratio Rint = (f12.7/f11.2)int = 0.377 ± 0.020. Conversely, the observed flux ratio, Robs = (f12.7/f11.2)obs, strongly correlates with the silicate strength (Ssil) confirming that differences in Robs reflect variation in τ. The relation between Robs and Ssil reproduces predictions for the Galactic Centre extinction law but disagrees with other laws. We calibrate the total extinction affecting the 11.2 μm PAH from Robs, which we apply to another sample of 215 galaxies with accurate measurements of the total infrared luminosity (LIR) to investigate the impact of extinction on L11.2/LIR. Correlation between L11.2/LIR and Robs independently on LIR suggests that increased extinction explains the well-known decrease in the average L11.2/LIR at high LIR. The extinction-corrected L11.2 is proportional to LIR in the range LIR = 109–1013 L⊙. These results consolidate L11.2 as a robust tracer of star formation in galaxies.
Structural, biochemical and functional analyses of tRNA-monooxygenase enzyme MiaE from Pseudomonas putida provide insights into tRNA/MiaE interaction
Authors: Carpentier Philippe , Leprêtre Chloé , Basset Christian , Douki Thierry , Torelli Stéphane , Duarte Victor , Hamdane Djemel , Fontecave Marc , Atta Mohamed
Published: July 2020

MiaE (2-methylthio-N6-isopentenyl-adenosine37-tRNA monooxygenase) is a unique non-heme diiron enzyme that catalyzes the O2-dependent post-transcriptional allylic hydroxylation of a hypermodified nucleotide 2-methylthio-N6-isopentenyl-adenosine (ms2i6A37) at position 37 of selected tRNA molecules to produce 2-methylthio-N6–4-hydroxyisopentenyl-adenosine (ms2io6A37). Here, we report the in vivo activity, biochemical, spectroscopic characterization and X-ray crystal structure of MiaE from Pseudomonas putida. The investigation demonstrates that the putative pp-2188 gene encodes a MiaE enzyme. The structure shows that Pp-MiaE consists of a catalytic diiron(III) domain with a four alpha-helix bundle fold. A docking model of Pp-MiaE in complex with tRNA, combined with site directed mutagenesis and in vivo activity shed light on the importance of an additional linker region for substrate tRNA recognition. Finally, krypton-pressurized Pp-MiaE experiments, revealed the presence of defined O2 site along a conserved hydrophobic tunnel leading to the diiron active center.
Visualization of the Thebesian veins during coronary angiography in a 57-year-old woman
Authors: Scoglio Martin , Cook Stéphane
Published: July 2020

A 57-year-old woman was hospitalized due to a type 2 respiratory failure. Electrocardiogram at admission showed inverted T waves in leads V2–V4. Coronary angiogram was performed showing no relevant stenosis. However, this exam allowed visualization of the Thebesian veins outlining the left ventricle.
Rapid and efficient mass collection by a supersonic cloud–cloud collision as a major mechanism of high-mass star formation
Authors: Fukui Yasuo , Inoue Tsuyoshi , Hayakawa Takahiro , Torii Kazufumi
Published: July 2020

A supersonic cloud–cloud collision produces a shock-compressed layer which leads to formation of high-mass stars via gravitational instability. We carried out a detailed analysis of the layer by using the numerical simulations of magneto-hydrodynamics which deal with colliding molecular flows at a relative velocity of 20 km s−1 (Inoue & Fukui 2013, ApJ, 774, L31). Maximum density in the layer increases from 1000 cm−3 to more than 105 cm−3 within 0.3 Myr by compression, and the turbulence and the magnetic field in the layer are amplified by a factor of ∼5, increasing the mass accretion rate by two orders of magnitude to more than 10−4 $ M_{\odot } $ yr−1. The layer becomes highly filamentary due to gas flows along the magnetic field lines, and dense cores are formed in the filaments. The massive dense cores have size and mass of 0.03–0.08 pc and 8–$ 50\, M_{\odot } $ and they are usually gravitationally unstable. The mass function of the dense cores is significantly top-heavy as compared with the universal initial mass function, indicating that the cloud–cloud collision preferentially triggers the formation of O and early B stars. We argue that the cloud–cloud collision is a versatile mechanism which creates a variety of stellar clusters from a single O star like RCW 120 and M 20 to tens of O stars of a super star cluster like RCW 38 and a mini-starburst W 43. The core mass function predicted by the present model is consistent with the massive dense cores obtained by recent ALMA observations in RCW 38 (Torii et al. 2021, PASJ, in press) and W 43 (Motte et al. 2018, Nature Astron., 2, 478). Considering the increasing evidence for collision-triggered high-mass star formation, we argue that cloud–cloud collision is a major mechanism of high-mass star formation.
Structuralism and Mathematical Practice in Felix Klein’s Work on Non-Euclidean Geometry†
Authors: Biagioli Francesca
Published: July 2020

It is well known that Felix Klein took a decisive step in investigating the invariants of transformation groups. However, less attention has been given to Klein’s considerations on the epistemological implications of his work on geometry. This paper proposes an interpretation of Klein’s view as a form of mathematical structuralism, according to which the study of mathematical structures provides the basis for a better understanding of how mathematical research and practice develop.
Improving Medical Students’ OSCE Performance in Telehealth: The Effects of a Telephone Medicine Curriculum
Authors: Hindman Daniel J. , Kochis Suzanne R. , Apfel Ariella , Prudent Joshua , Kumra Tina , Golden W. Christopher , Jung Julianna , Pahwa Amit K.
Published: July 2020

Purpose

To report on the implementation of a telephone medicine curriculum as part of the core clerkship in pediatrics for students at Johns Hopkins University School of Medicine and evaluate the curriculum’s effect on student performance on a telephone medicine case as part of a required objective structured clinical exam (OSCE).

Method

Using a prospective cohort design with a convenience sample of third-year medical students during the 2016–2017 and 2017–2018 academic years, the authors compared the OSCE scores of students assigned to the curriculum with both historical and concurrent control groups of students who had not received the curriculum. Additionally, the authors compared the costs of the recommended testing by students in each group using the 2018 Centers for Medicare and Medicaid Services Clinical Laboratory Fee Schedule.

Results

Students assigned to the telephone medicine curriculum (students in the intervention group) had a significantly higher mean overall score on the simulated OSCE telephone medicine case compared with the students in the control groups who did not receive the curriculum (the mean score for students in the intervention group was 7.38 vs 6.92 for students in the control groups, P = .02). Additionally, the intervention group had statistically significantly lower costs for their recommended testing compared with the control groups (the median value for tests ordered by students in the intervention group was $27.91 vs $51.23 for students in the control groups, P = .03).

Conclusions

Implementing a dedicated telephone medicine curriculum for medical students improves their overall performance and delivery of high-value care via telephone medicine as part of an OSCE. Medical educators should pursue ongoing research into effective methods for teaching medical students and residents how to navigate digital encounters.
Death-associated Protein Kinase 1 Mediates Ventilator-induced Lung Injury in Mice by Promoting Alveolar Epithelial Cell Apoptosis
Authors: Wang Yaxin , Yang Yiyi , Chen Lin , Xiong Wei , Song Limin , Li Bo , Zhou Ting , Pei Lei , Yuan Shiying , Yao Shanglong , Shang You
Published: July 2020

Background

Alveolar epithelial cell apoptosis is implicated in the onset of ventilator-induced lung injury. Death-associated protein kinase 1 (DAPK1) is associated with cell apoptosis. The hypothesis was that DAPK1 participates in ventilator-induced lung injury through promoting alveolar epithelial cell apoptosis.

Methods

Apoptosis of mouse alveolar epithelial cell was induced by cyclic stretch. DAPK1 expression was altered (knockdown or overexpressed) in vitro by using a small interfering RNA or a plasmid, respectively. C57/BL6 male mice (n = 6) received high tidal volume ventilation to establish a lung injury model. Adeno-associated virus transfection of short hairpin RNA and DAPK1 inhibitor repressed DAPK1 expression and activation in lungs, respectively. The primary outcomes were alveolar epithelial cell apoptosis and lung injury.

Results

Compared with the control group, the 24-h cyclic stretch group showed significantly higher alveolar epithelial cell apoptotic percentage (45 ± 4% fold vs. 6 ± 1% fold; P < 0.0001) and relative DAPK1 expression, and this group also demonstrated a reduced apoptotic percentage after DAPK1 knockdown (27 ± 5% fold vs. 53 ± 8% fold; P < 0.0001). A promoted apoptotic percentage in DAPK1 overexpression was observed without stretching (49 ± 6% fold vs. 14 ± 3% fold; P < 0.0001). Alterations in B-cell lymphoma 2 and B-cell lymphoma 2–associated X are associated with DAPK1 expression. The mice subjected to high tidal volume had higher DAPK1 expression and alveolar epithelial cell apoptotic percentage in lungs compared with the low tidal volume group (43 ± 6% fold vs. 4 ± 2% fold; P < 0.0001). Inhibition of DAPK1 through adeno-associated virus infection or DAPK1 inhibitor treatment appeared to be protective against lung injury with reduced lung injury score, resolved pulmonary inflammation, and repressed alveolar epithelial cell apoptotic percentage (47 ± 4% fold and 48 ± 6% fold; 35 ± 5% fold and 34 ± 4% fold; P < 0.0001, respectively).

Conclusions

DAPK1 promotes the onset of ventilator-induced lung injury by triggering alveolar epithelial cell apoptosis through intrinsic apoptosis pathway in mice.

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Peripheral Auditory Involvement in Childhood Listening Difficulty
Authors: Hunter Lisa L. , Blankenship Chelsea M. , Lin Li , Sloat Nicholette T. , Perdew Audrey , Stewart Hannah , Moore David R.
Published: July 2020

Objectives:

This study tested the hypothesis that undetected peripheral hearing impairment occurs in children with idiopathic listening difficulties (LiDs), as reported by caregivers using the Evaluation of Children”s Listening and Processing Skills (ECLiPS) validated questionnaire, compared with children with typically developed (TD) listening abilities.

Design:

Children with LiD aged 6–14 years old (n = 60, mean age = 9.9 yr) and 54 typical age matched children were recruited from audiology clinical records and from IRB-approved advertisements at hospital locations and in the local and regional areas. Both groups completed standard and extended high-frequency (EHF) pure-tone audiometry, wideband absorbance tympanometry and middle ear muscle reflexes, distortion product and chirp transient evoked otoacoustic emissions. Univariate and multivariate mixed models and multiple regression analysis were used to examine group differences and continuous performance, as well as the influence of demographic factors and pressure equalization (PE) tube history.

Results:

There were no significant group differences between the LiD and TD groups for any of the auditory measures tested. However, analyses across all children showed that EHF hearing thresholds, wideband tympanometry, contralateral middle ear muscle reflexes, distortion product, and transient-evoked otoacoustic emissions were related to a history of PE tube surgery. The physiologic measures were also associated with EHF hearing loss, secondary to PE tube history.

Conclusions:

Overall, the results of this study in a sample of children with validated LiD compared with a TD group matched for age and sex showed no significant differences in peripheral function using highly sensitive auditory measures. Histories of PE tube surgery were significantly related to EHF hearing and to a range of physiologic measures in the combined sample.