bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing aminoglycoside selection for KPC-producing Klebsiella pneumoniae with the aminoglycoside-modifying enzyme (AME) gene aac(6’)-Ib
Authors: Butler David A , Rana Amisha P , Krapp Fiorella , Patel Shitalben R , Huang Yanqin , Ozer Egon A , Hauser Alan R , Bulman Zackery P
Published: October 2020

Objectives

KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates commonly co-harbour the aminoglycoside-modifying enzyme (AME) gene aac(6’)-Ib, which encodes an AME that can confer resistance to some of the commercially available aminoglycosides. We sought to determine the influence of AAC(6’)-Ib in KPC-Kp on the pharmacodynamic activity of aminoglycosides.

Methods

Six KPC-Kp clinical isolates, three with and three without aac(6’)-Ib, were analysed. Using these isolates, the bacterial killing of amikacin, gentamicin and tobramycin was assessed in static time–kill experiments. The pharmacodynamic activity of the aminoglycosides was then assessed in a dynamic one-compartment infection model over 72 h using simulated human pharmacokinetics of once-daily dosing with amikacin (15 mg/kg), gentamicin (5 mg/kg) and tobramycin (5 mg/kg).

Results

At clinically relevant aminoglycoside concentrations in time–kill experiments and the dynamic one-compartment model, gentamicin was more active than amikacin or tobramycin against the isolates harbouring aac(6’)-Ib. Amikacin, gentamicin and tobramycin all showed progressively reduced bacterial killing with exposure to repeated doses against most isolates in the dynamic one-compartment model. MIC values were generally not a good predictor of gentamicin pharmacodynamic activity against KPC-Kp, but were more reliable for amikacin and tobramycin.

Conclusions

Gentamicin may be preferred over amikacin or tobramycin for treatment of KPC-Kp infections. However, gentamicin MICs are not a consistent predictor of its pharmacodynamic activity and unexpected treatment failures are possible.
Persistent inequitable design and implementation of patient portals for users at the margins
Authors: Goedhart Nicole S , Zuiderent-Jerak Teun , Woudstra Joey , Broerse Jacqueline E W , Betten Afke Wieke , Dedding Christine
Published: October 2020

Objective

Diane Forsythe and other feminist scholars have long shown how system builders’ tacit assumptions lead to the systematic erasure of certain users from the design process. In spite of this phenomena being known in the health informatics literature for decades, recent research shows how patient portals and electronic patients health records continue to reproduce health inequalities in Western societies. To better understand this discrepancy between scholarly awareness of such inequities and mainstream design, this study unravels the (conceptual) assumptions and practices of designers and others responsible for portal implementation in the Netherlands and how citizens living in vulnerable circumstances are included in this process.

Materials and methods

We conducted semistructured interviews (n = 24) and questionnaires (n = 14) with portal designers, health professionals, and policy advisors.

Results

In daily design practices, equity is seen as an “end-of-the-pipeline” concern. Respondents identify health care professionals rather than patients as their main users. If patients are included in the design, this generally entails patients in privileged positions. The needs of citizens living in vulnerable circumstances are not prioritized in design processes. Developers legitimize their focus with reference to the innovation-theoretical approach of the Diffusion of Innovations.

Discussion and conclusion

Although feminist scholars have developed important understandings of the exclusion of citizens living in vulnerable circumstances from portal design, other academic efforts have profoundly shaped daily practices of portal development. Diane Forsythe would likely have taken up this discrepancy as a challenge by finding ways to translate these insights into mainstream systems design.
Patient-centered care and the electronic health record: exploring functionality and gaps
Authors: Butler Jorie M , Gibson Bryan , Lewis Lacey , Reiber Gayle , Kramer Heidi , Rupper Rand , Herout Jennifer , Long Brenna , Massaro David , Nebeker Jonathan
Published: October 2020

Objective

Healthcare systems have adopted electronic health records (EHRs) to support clinical care. Providing patient-centered care (PCC) is a goal of many healthcare systems. In this study, we sought to explore how existing EHR systems support PCC; defined as understanding the patient as a whole person, building relational connections between the clinician and patient, and supporting patients in health self-management.

Materials and Methods

We assessed availability of EHR functions consistent with providing PCC including patient goals and preferences, integrated care plans, and contextual and patient-generated data. We surveyed and then interviewed technical representatives and expert clinical users of 6 leading EHR systems. Questions focused on the availability of specific data and functions related to PCC (for technical representatives) and the clinical usefulness of PCC functions (for clinicians) in their EHR.

Results

Technical representatives (n = 6) reported that patient communication preferences, personalized indications for medications, and end of life preferences were functions implemented across 6 systems. Clinician users (n = 10) reported moderate usefulness of PCC functions (medians of 2–4 on a 5-pointy -35t scale), suggesting the potential for improvement across systems. Interviews revealed that clinicians do not have a shared conception of PCC. In many cases, data needed to deliver PCC was available in the EHR only in unstructured form. Data systems and functionality to support PCC are under development in these EHRs.

Discussion and Conclusion

There are current gaps in PCC functionality in EHRs and opportunities to support the practice of PCC through EHR redesign.
Genetic association among feeding behavior, feed efficiency, and growth traits in growing indicine cattle
Authors: Benfica Lorena Ferreira , Sakamoto Leandro Sannomiya , Magalhães Ana Fabrícia Braga , de Oliveira Matheus Henrique Vargas , de Albuquerque Lúcia Galvão , Cavalheiro Roberto , Branco Renata Helena , Cyrillo Joslaine Noely dos Santos Goncalves , Mercadante Maria Eugênia Zerlotti
Published: October 2020

This study aimed to estimate genetic parameters, including genomic data, for feeding behavior, feed efficiency, and growth traits in Nellore cattle. The following feeding behavior traits were studied (861 animals with records): time spent at the feed bunk (TF), duration of one feeding event (FD), frequency of visits to the bunk (FF), feeding rate (FR), and dry matter intake (DMI) per visit (DMIv). The feed efficiency traits (1,543 animals with records) included residual feed intake (RFI), residual weight gain (RWG), and feed conversion (FC). The growth traits studied were average daily gain (ADG, n = 1,543 animals) and selection (postweaning) weight (WSel, n = 9,549 animals). The (co)variance components were estimated by the maximum restricted likelihood method, fitting animal models that did (single-step genomic best linear unbiased prediction) or did not include (best linear unbiased prediction) genomic information in two-trait analyses. The direct responses to selection were calculated for the feed efficiency traits, ADG, and WSel, as well as the correlated responses in feed efficiency and growth by direct selection for shorter TF. The estimated heritabilities were 0.51 ± 0.06, 0.35 ± 0.06, 0.27 ± 0.07, 0.34 ± 0.06, and 0.33 ± 0.06 for TF, FD, FF, FR, and DMIv, respectively. In general, TF and FD showed positive genetic correlations with all feed efficiency traits (RFI, RWG, and FC), ADG, DMI, and WSel. Additionally, TF showed high and positive genetic and phenotypic correlations with RFI (0.71 ± 0.10 and 0.46 ± 0.02, respectively) and DMI (0.56 ± 0.09 and 0.48 ± 0.03), and medium to weak genetic correlations with growth (0.32 ± 0.11 with ADG and 0.14 ± 0.09 with WSel). The results suggest that TF is a strong indicator trait of feed efficiency, which exhibits high heritability and a weak positive genetic correlation with growth. In a context of a selection index, the inclusion of TF to select animals for shorter TF may accelerate the genetic gain in feed efficiency by reducing RFI but with zero or slightly negative genetic gain in growth traits.
Visualization of endogenous nuclear F-actin in mouse embryos reveals abnormal actin assembly after somatic cell nuclear transfer
Authors: Shindo Taiki , Ihashi Shunya , Sakamoto Yuko , Okuno Tomomi , Tomikawa Junko , Miyamoto Kei
Published: October 2020

Actin in the nucleus, referred to as nuclear actin, is involved in a variety of nuclear events. Nuclear actin is present as a globular (G-actin) and filamentous form (F-actin), and dynamic assembly/disassembly of nuclear actin profoundly affects nuclear functions. However, it is still challenging to observe endogenous nuclear F-actin. Here, we present a condition to visualize endogenous nuclear F-actin of mouse zygotes using different fixation methods. Zygotes fixed with paraformaldehyde and treated with fluorescently conjugated phalloidin show both short and long actin filaments in their pronuclei. Short nuclear actin filaments are characteristic of phalloidin staining, rather than the consequence of severing actin filaments by the fixation process, since long nuclear actin filaments probed with the nuclear actin chromobody are not disassembled into short filaments after fixation with paraformaldehyde. Furthermore, we find that nuclear actin assembly is impaired after somatic cell nuclear transfer (SCNT), suggesting abnormal nucleoskeleton structures in SCNT embryos. Taken together, our presented method for visualizing nuclear F-actin with phalloidin can be used to observe the states of nuclear actin assembly, and revealed improper reprogramming of actin nucleoskeleton structures in cloned mouse embryos.
Vacuum Steam Treatment Effectiveness for Eradication of the Thousand Cankers Disease Vector and Pathogen in Logs From Diseased Walnut Trees
Authors: Juzwik Jennifer , Yang Anna , Heller Sarah , Moore Melanie , Chen Zhangjing , White Marshall , Wantuch Holly , Ginzel Matthew , Mack Ron
Published: October 2020

Logs of high-value eastern black walnut (Juglans nigra L.) are commonly exported from the United States for production of veneer and lumber. Veneer logs are not debarked to minimize degradation of wood quality and reduce moisture loss. Thousand cankers disease (TCD) is caused by the walnut twig beetle (Pityophthorus juglandis Blackman) and the fungal pathogen, Geosmithia morbida M. Kolarik, E. Freeland, C. Utley and N. Tisserat sp. nov., which colonize the inner bark of Juglans species. Effective eradication of these organisms by heat or chemical fumigation treatment is required for walnut logs prior to export. Because vacuum steam is an effective and efficient means of heating round wood, its use in eliminating the TCD causal agents was evaluated using Juglans logs (12- to 44-cm small end diameter and 1.7- to 1.9-m length) from TCD-symptomatic trees in Oregon and Washington State. Five replicate trials with three logs per load were conducted in a portable vacuum chamber to test two treatment schedules: 60°C for 60 min and 56°C for 30 min. Complete elimination of P. juglandis and G. morbida was achieved when using a minimum of 56°C at 5-cm targeted depth from bottom of bark furrow into the sapwood and held for 30 min. Treatment cycle time ranged from 298 to 576 min depending on log diameter and initial log temperature. Artificial inoculation of J. nigra trees with G. morbida within the TCD range in Pennsylvania was minimally successful in producing adequately colonized logs for experimental trials.
Generation-Dependent Functional and Numerical Responses of a Naturally Fungus-Infected Colony ofHabrobracon hebetor(Hymenoptera: Braconidae) Reared onEphestia kuehniella(Lepidoptera: Pyralidae) in Iran
Authors: Badran Fatima , Fathipour Yaghoub , Bagheri Abdoolnabi , Attaran Mohammadreza , Reddy Gadi V P
Published: October 2020

The functional and numerical responses of Habrobracon hebetor (Say) were assessed over 30 sequential generations (G) on different densities (2, 4, 8, 16, 32, 64, and 128 fifth-instar larvae) of the Mediterranean flour moth, Ephestia kuehniella (Zeller). Seven tested generations (G2inf, G4inf, G6inf, G8inf, G10inf, G15inf, and G30inf) had already been naturally infected by a fungus species, whereas only the second generation (G2) had the colonies of both infected (G2inf) and uninfected (G2uninf) individuals. All infected generations, as well as the uninfected generation, showed a Type III functional response. A high variation was found in the handling times (Th) of the parasitoid through 30 sequential generations, and G10inf had the longest handling time. The shortest handling time and the maximum estimated attack rate (T/Th) were observed in G2inf. No significant difference in terms of the number of parasitized hosts was found among all infected generations, as well as between G2inf and G2uninf. Although the handling times in G2inf and G2uninf were close to each other, the attack coefficient of G2uninf was more than that of G2inf. The attack coefficient and handling time of infected generations increased from G2inf to G10inf and then decreased in the higher generations. The most plausible parameters of functional response of infected generations were observed in Ginf. A negative relationship between eggs laid and host densities was observed in the infected generations (G2inf, G4inf, G6inf, G8inf, and G10inf). G2uninf and, among infected generations, Ginf were the best generations for practical utilization in inundative release programs.
Validity of the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) for Japanese patients with labral tear
Authors: Watanabe Nobuyuki , Murakami Satona , Uchida Soshi , Tateishi Satoshi , Ohara Hidetsugu , Yamamoto Yasuhiro , Kojima Taiki ,   JAHORN (Japan Arthroscopy of the Hip Outcomes Research Network)
Published: October 2020

The Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) was created for patient-reported outcome measures (PROMs) and to evaluate the conditions of patients with hip disease. Nevertheless, the validity of the JHEQ for patients with hip labral tears remains unclear. Therefore, we validated the JHEQ in patients with labral tears. There were 51 patients (mean age 44.5, range 18–60 years; 31 women). Thirty-two patients had right-sided tears, 29 underwent hip arthroscopy, 32 had femoroacetabular impingement and 15 had developmental hip dysplasia. Five PROMs included in the JHEQ were evaluated using test–retest methods. Statistical analysis was performed using SPSS software according to the COnsensus-based Standards for the selection of health status Measurement Instruments checklist. The intra-class correlation coefficient (1, 2) of all JHEQ scores (84 points) was 0.88 and Cronbach’s α was 0.94. Bland–Altman analysis revealed good test–retest reliability for the JHEQ. The Spearman’s rank test, including the SF-36 subscale, showed a high correlation with physical functioning [1, 0.67 (P < 0.01); 2, 0.65 (P < 0.01)], body pain [1, 0.54 (P < 0.01); 2, 0.53 (P < 0.01)] and physical component summary [1, 0.55 (P < 0.01); 2, 0.55 (P < 0.01)]. The value of minimal important change (22.9) was higher than that of smallest detectable change (3.21), suggesting that the JHEQ has adequate responsiveness. We demonstrated the reliability, validity and responsiveness of the JHEQ in Japanese patients with hip labral tears. JHEQ is a valid assessment tool not only for patients with hip osteoarthritis or osteonecrosis but also for those with hip labral tears.
Refugee and Asylum-Seeking Children in Mae Sot and Bangkok: An Analysis of Unmet Needs and Risks
Authors: Thoresen Paradee , Gillieatt Sue , Fielding Angela
Published: October 2020

This article reports on a longitudinal case study, which included site visits in Thailand from 2014 to 2015, and participant follow-up to mid-2018. It documents the lived experience of children from Syria, Sri Lanka, Pakistan, Vietnam, and Myanmar in two different locations in Thailand: Bangkok and Mae Sot (a district close to Thailand-Myanmar border with a long history of economic migrants and refugees from Myanmar). It documents perspectives of children and the adults in their lives while in exile. It presents an analysis of the children’s perspectives on needs and how unmet needs for safety, basic materials, health care, and education put them at risk of arrest, detention, abuse, and exploitation, and impact their psychological development. Contextual factors such as available services, existing policies and laws are also discussed in relation to the Convention on the Rights of the Child (CRC).
On the mechanism of polarized metre-wave stellar emission
Authors: Vedantham H K
Published: October 2020

Two coherent radio emission mechanisms operate in stellar coronae: plasma emission and cyclotron emission. They directly probe the electron density and magnetic field strength respectively. Most stellar radio detections have been made at cm-wavelengths where it is often not possible to uniquely identify the emission mechanism, hindering the utility of radio observations in probing coronal conditions. In anticipation of stellar observations from a suite of sensitive low-frequency ($\nu \sim 10^2\, {\rm MHz}$) radio telescopes, here I apply the general theory of coherent emission in non-relativistic plasma to the low-frequency case. I consider the recently reported low-frequency emission from dMe flare stars AD Leo and UV Ceti and the quiescent star GJ 1151 as test cases. My main conclusion is that unlike the cm-wave regime, for reasonable turbulence saturation regimes, the emission mechanism in metre-wave observations ($\nu \sim 10^2\, {\rm MHz}$) can often be identified based on the observed brightness temperature, emission duration, and polarization fraction. I arrive at the following heuristic: M-dwarf emission that is ≳ hour-long with ${\gtrsim}50{{\ \rm per\ cent}}$ circular polarized fraction at brightness temperatures of ${\gtrsim}10^{12}\,$K at ${\sim}100\, {\rm MHz}$ in M-dwarfs strongly favours a cyclotron maser interpretation.
New optically identified supernova remnants in the Large Magellanic Cloud
Authors: Yew Miranda , Filipović Miroslav D , Stupar Milorad , Points Sean D , Sasaki Manami , Maggi Pierre , Haberl Frank , Kavanagh Patrick J , Parker Quentin A , Crawford Evan J , Vukotić Branislav , Urošević Dejan , Sano Hidetoshi , Seitenzahl Ivo R , Rowell Gavin , Leahy Denis , Bozzetto Luke M , Maitra Chandreyee , Leverenz Howard , Payne Jeffrey L , Park Laurence A F , Alsaberi Rami Z E , Pannuti Thomas G
Published: October 2020

We present a new optical sample of three Supernova Remnants (SNRs) and 16 Supernova Remnant (SNR) candidates in the Large Magellanic Cloud (LMC). These objects were originally selected using deep H α, [S ii], and [O iii] narrow-band imaging. Most of the newly found objects are located in less dense regions, near or around the edges of the LMC’s main body. Together with previously suggested MCSNR J0541–6659, we confirm the SNR nature for two additional new objects: MCSNR J0522–6740 and MCSNR J0542–7104. Spectroscopic follow-up observations for 12 of the LMC objects confirm high [S ii]/H α emission-line ratios ranging from 0.5 to 1.1. We consider the candidate J0509–6402 to be a special example of the remnant of a possible type Ia Supernova (SN) which is situated some 2° (∼1.75 kpc) north from the main body of the LMC. We also find that the SNR candidates in our sample are significantly larger in size than the currently known LMC SNRs by a factor of ∼2. This could potentially imply that we are discovering a previously unknown but predicted, older class of large LMC SNRs that are only visible optically. Finally, we suggest that most of these LMC SNRs are residing in a very rarefied environment towards the end of their evolutionary span where they become less visible to radio and X-ray telescopes.
Refeeding syndrome as described in 1507 by Antonio Benivieni in Florence
Authors: De Santo Natale G , Bisaccia Carmela , Phillips Malcolm E , De Santo Luca S
Published: October 2020

In 1981, Weinsier and Krumdieck described death resulting from overzealous total parenteral nutrition in two chronically malnourished, but stable, patients given aggressive total parenteral nutrition. This was the birth of what is now called the refeeding syndrome, a nutrition-related disorder associated with severe electrolyte disturbances.

The purpose of this work is to demonstrate that refeeding syndrome was first described medically in Florence by Antonio Benivieni in 1507 in his book On Some Hidden and Remarkable Causes of Diseases and Cures.

What we now know as refeeding syndrome was described in Report No. LVII of that book. The condition occurred as a result of the famine that affected Florence in 1496. The report documents (i) death due to starvation, (ii) death due to ingestion of deteriorated/toxic foods (inevitable in times of famine when healthy food is scarce), (iii) death caused by excessive food ingestion after forced, prolonged abstinence from food in adults, (iv) the death of breast-fed children and of their starved mothers eating to satiety and (v) the more favourable clinical outcome of those admitted to hospitals.

It is possible that Benivieni was inspired by the description of the deaths of starved deserters in the book The Jewish War (70 AD) by the Romano-Jewish historian Flavius Josephus. Nevertheless, Benivieni wrote the first medical account of the central clinical features of refeeding syndrome. The main, broad clinical aspects of refeeding syndrome, described by Weinsier and Krumdieck in 1981, had been documented in medical literature four centuries earlier by Benivieni.
Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033-26033
Authors: Klein Martin , Drijver A Josephine , van den Bent Martin J , Bromberg Jacolien C , Hoang-Xuan Khê , Taphoorn Martin J B , Reijneveld Jaap C , Ben Hassel Mohamed , Vauleon Elodie , Eekers Daniëlle B P , Tzuk-Shina Tzahala , Lucas Anna , Freixa Salvador Villà , Golfinopoulos Vasilis , Gorlia Thierry , Hottinger Andreas F , Stupp Roger , Baumert Brigitta G
Published: October 2020

Background

EORTC study 22033–26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning.

Methods

Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time.

Results

Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes.

Conclusion

In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.
Universal Polymerase Chain Reaction and Antibody Testing Demonstrate Little to No Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in a Rural Community
Authors: Appa Ayesha , Takahashi Saki , Rodriguez-Barraquer Isabel , Chamie Gabriel , Sawyer Aenor , Duarte Elias , Hakim Jill , Turcios Keirstinne , Vinden Joanna , Janson Owen , Manglik Aashish , Peluso Michael J , Deeks Steven G , Henrich Timothy J , Torres Leonel , Rodgers Mary , Hackett John , Chiu Charles , Havlir Diane , Greenhouse Bryan
Published: October 2020

Background

Limited systematic surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the early months of the US epidemic curtailed accurate appraisal of transmission intensity. Our objective was to perform case detection of an entire rural community to quantify SARS-CoV-2 transmission using polymerase chain reaction (PCR) and antibody testing.

Methods

We conducted a cross-sectional survey of SARS-CoV-2 infection in the rural town of Bolinas, California (population 1620), 4 weeks after shelter-in-place orders. Participants were tested between April 20 and 24, 2020. Prevalence by PCR and seroprevalence from 2 forms of antibody testing were performed in parallel (Abbott ARCHITECT immunoglobulin [Ig]G and in-house IgG enzyme-linked immunosorbent assay).

Results

Of 1891 participants, 1312 were confirmed Bolinas residents (>80% community ascertainment). Zero participants were PCR positive. Assuming 80% sensitivity, it would have been unlikely to observe these results (P < .05) if there were >3 active infections in the community. Based on antibody results, estimated prevalence of prior infection was 0.16% (95% credible interval [CrI], 0.02%–0.46%). The positive predictive value (PPV) of a positive result on both tests was 99.11% (95% CrI, 95.75%–99.94%), compared with PPV 44.19%–63.32% (95% CrI, 3.25%–98.64%) if 1 test was utilized.

Conclusions

Four weeks after shelter-in-place, SARS-CoV-2 infection in a rural Northern California community was extremely rare. In this low-prevalence setting, use of 2 antibody tests increased seroprevalence estimate precision. This was one of the first community-wide studies to successfully implement synchronous PCR and antibody testing, particularly in a rural setting. Widespread testing remains an underpinning of effective disease control in conjunction with consistent uptake of public health measures.
Predictors of subclinical systemic sclerosis primary heart involvement characterised by microvasculopathy and myocardial fibrosis
Authors: Dumitru Raluca B , Bissell Lesley-Anne , Erhayiem Bara , Fent Graham , Kidambi Ananth , Swoboda Peter , Abignano Giuseppina , Donica Helena , Burska Agata , Greenwood John P , Biglands John , Del Galdo Francesco , Plein Sven , Buch Maya H
Published: October 2020

Objectives

SSc primary heart involvement (SSc-pHI) is a significant cause of mortality. We aimed to characterize and identify predictors of subclinical SSc-pHI using cardiovascular MRI.

Methods

A total of 83 SSc patients with no history of cardiovascular disease or pulmonary arterial hypertension and 44 healthy controls (HCs) underwent 3 Tesla contrast-enhanced cardiovascular MRI, including T1 mapping and quantitative stress perfusion. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide were also measured.

Results

Cardiovascular MRI revealed a lower myocardial perfusion reserve in the SSc patients compared with HCs {median (interquartile range (IQR)] 1.9 (1.6–2.4) vs 3 (2–3.6), P < 0.001}. Late gadolinium enhancement, indicating focal fibrosis, was observed in 17/83 patients but in none of the HCs, with significantly higher extracellular volume (ECV), suggestive of diffuse fibrosis, in SSc vs HC [mean (s.d.) 31 (4) vs 25 (2), P < 0.001]. Presence of late gadolinium enhancement and higher ECV was associated with skin score [odds ratio (OR) = 1.115, P = 0.048; R2 = 0.353, P = 0.004], and ECV and myocardial perfusion reserve was associated with the presence of digital ulcers at multivariate analysis (R2 = 0.353, P < 0.001; R2 = 0.238, P = 0.011). High-sensitivity troponin I was significantly higher in patients with late gadolinium enhancement, and N-terminal pro-brain natriuretic peptide was associated with ECV (P < 0.05).

Conclusion

Subclinical SSc-pHI is characterized by myocardial microvasculopathy, diffuse and focal myocardial fibrosis but preserved myocardial contractile function. This subclinical phenotype of SSc-pHI was associated with high-sensitivity troponin I, N-terminal pro-brain natriuretic peptide, SSc disease severity and complicated peripheral vasculopathy. These data provide information regarding the underlying pathophysiological processes and provide a basis for identifying individuals at risk of SSc-pHI.
Acute and Subacute Oral Toxicity of Deoxynivalenol Exposure in aDermatophagoides farinae-Induced Murine Asthma Model
Authors: Ookawara Toa , Aihara Ryota , Morimoto Ai , Iwashita Naoki , Kurata Keigo , Takagi Yoshiichi , Miyasaka Atsushi , Kushiro Masayo , Miyake Shiro , Fukuyama Tomoki
Published: October 2020

Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen (Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1β, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy.
Phylogenetic revision of the shrimp generaEphyrina,MeningodoraandNotostomus(Acanthephyridae: Caridea)
Authors: Lunina Anastasiia A , Kulagin Dmitry N , Vereshchaka Alexander L
Published: October 2020

The shrimp genera Ephyrina, Meningodora and Notostomus have an unusual carapace strengthened with carinae and a half-serrated mandible, which may suggest a possible monophyly of this group. Here we test this hypothesis and present the first phylogenetic study of these genera based on 95 morphological characters (all valid species coded) and six molecular markers (71% of valid species sequenced). Representatives of all genera of Oplophoridae (sister to Acanthephyridae) were outgroups, 32 species belonging to all genera and potentially different clades of Acanthephyridae were ingroups. Both morphological and molecular analyses retrieve trees with similar topology. Our results reject the hypothesis of a clade formed by Ephyrina + Meningodora + Notostomus. We show that Ephyrina and Notostomus are monophyletic, both on morphological and on molecular trees, Meningodora gains support only on morphological trees. Evolutionary traits in the Ephyrina and Meningodora + Notostomus clades are different. Synapomorphies are mostly linked to adaptations to forward motion in Ephyrina (oar-like meri and ischia of pereopods, stempost-like rostrum) and to progressive strengthening of the carapace and pleon in Meningodora and Notostomus (net of sharp carinae). Unusual mandibles evolved in the clades independently and represent convergent adaptations to feeding on gelatinous organisms.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section
Authors: Kim Hye Jin , Choi Yong Seon , Kim Seung Hyun , Lee Wootaek , Kwon Ja-Young , Kim Do-Hyeong
Published: October 2020

BACKGROUND

Spinal anaesthesia-induced hypotension is frequently reported in patients undergoing caesarean section. Mechanistically, sympathetic blockade reduces the systemic vascular resistance and the left ventricular preload, causing hypotension, which is augmented by aortocaval compression. The corrected blood flow time (FTc) is affected by the preload and is inversely related to the afterload.

OBJECTIVE

We hypothesised that the preanaesthetic carotid artery FTc could predict hypotension after induction in patients undergoing a caesarean section with spinal anaesthesia.

DESIGN

A prospective observational study.

SETTING

A tertiary referral centre in South Korea from September 2018 to November 2019.

PARTICIPANTS

Thirty-eight parturients scheduled for elective caesarean section under spinal anaesthesia.

INTERVENTIONS

Using carotid ultrasonography, FTc was measured twice prior to inducing spinal anaesthesia. FTc was calculated using both Bazett's (B) and Wodey's (W) formulae. Hypotension was defined as an SBP decrease to less than 80 mmHg, or less than 75% of baseline, or if symptoms consistent with hypotension occurred from the time of injection of the spinal anaesthetic until delivery.

MAIN OUTCOME MEASURES

The primary endpoint was to determine the predictive value of preanaesthetic FTc for postspinal hypotension during caesarean delivery.

RESULTS

Among the 35 patients who completed this study, hypotension occurred in 21 (60%). The areas under the receiver-operating characteristic curves for FTc (B) and FTc (W) were 0.905 [95% confidence interval (CI), 0.757 to 0.978, P < 0.001] and 0.922 (95% CI, 0.779 to 0.985, P < 0.001), respectively. The optimal cut-off values for predicting hypotension were 346.4 and 326.9 ms, respectively. The grey zone for FTc (B) and FTc (W) included 40 and 14% of the patients, respectively.

CONCLUSION

Preanaesthetic carotid artery FTc was a reliable indicator of postspinal hypotension in parturients. Considering the grey zone, Wodey's formula is better than Bazett's formula.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03631329.
t(1;22)(p13;q13) Acute Megakaryoblastic Leukemia Complicated by Hepatic Fibrosis: Antifibrosis Therapy?
Authors: Feng Jianhua , Leung Alex W.K. , Cheng Frankie W.T. , Lam Grace K.S. , Chow Terry T.W. , Ng Margaret H.L. , Chu Winnie C.W. , Chan Natalie P.H. , Li Chi-kong
Published: October 2020

Background:

There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis.

Observation:

Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years.

Conclusions:

Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis.
A Multicentric Comparison of Apparent Diffusion Coefficient Mapping and the Kaiser Score in the Assessment of Breast Lesions
Authors: Dietzel Matthias , Krug Barbara , Clauser Paola , Burke Christina , Hellmich Martin , Maintz David , Uder Michael , Bickel Hubert , Helbich Thomas , Baltzer Pascal A.T.
Published: October 2020

Objective

We sought to compare the diagnostic performance of apparent diffusion coefficient (ADC) mapping with the Kaiser score (KS) to distinguish benign from malignant breast lesions and to assess the potential of this approach to help avoid unnecessary biopsies.

Materials and Methods

In this multicentric study, individual patient data from 3 different centers were analyzed. Consecutive patients receiving standardized multiparametric breast magnetic resonance imaging for standard nonscreening indications were included. At each center, 2 experienced radiologists with more than 5 years of experience retrospectively interpreted the examinations in consensus and applied the KS to every histologically verified lesion. The corresponding mean ADC of each lesion was measured using a Wielema type 4 region of interest. According to established methods, the KS and ADC were combined, yielding the KS+ score. Diagnostic accuracy was evaluated by the area under the receiver operating characteristics curve (AUROC) and compared between the KS, ADC, and KS+ (DeLong test). Likewise, the potential to help avoid unnecessary biopsies was compared between the KS, ADC, and KS+ based on established high sensitivity thresholds (McNemar test).

Results

A total of 450 lesions in 414 patients (mean age, 51.5 years; interquartile range, 42–60.8 years) were included, with 219 lesions being malignant (48.7%; 95% confidence interval [CI], 44%–53.4%). The performance of the KS (AUROC, 0.915; CI, 0.886–0.939) was significantly better than that of the ADC (AUROC, 0.848; CI, 0.811–0.880; P < 0.001). The largest difference between these parameters was observed when assessing subcentimeter lesions (AUROC, 0.909 for KS; CI, 0.849–0.950 vs 0.811 for ADC; CI, 0.737–0.871; P = 0.02).

The use of the KS+ (AUROC, 0.918; CI, 0.889–0.942) improved the performance slightly, but without any significant difference relative to a single KS or ADC reading (P = 0.64).

When applying high sensitivity thresholds for avoiding unnecessary biopsies, the KS and ADC achieved equal sensitivity (97.7% for both; cutoff values, >4 for KS and ≤1.4 × 10−3 mm2/s for ADC). However, the rate of potentially avoidable biopsies was higher when using the KS (specificity: 65.4% for KS vs 32.9% for ADC; P < 0.0001). The KS was superior to the KS+ in avoiding unnecessary biopsies.

Conclusions

Both the KS and ADC may be used to distinguish benign from malignant breast lesions. However, KS proved superior in this task including, most of all, when assessing small lesions less than 1 cm. Using the KS may avoid twice as many unnecessary biopsies, and the combination of both the KS and ADS does not improve diagnostic performance.
A Gratifying Step forward for the Application of Artificial Intelligence in the Field of Endoscopy: A Narrative Review
Authors: Xu Yixin , Tan Yulin , Wang Yibo , Gao Jie , Wu Dapeng , Xu Xuezhong
Published: October 2020

Background:

Endoscopy is the optimal choice of diagnosis of gastrointestinal (GI) diseases. Following the advancements made in medical technology, different kinds of novel endoscopy-methods have emerged. Although the significant progress in the penetration of endoscopic tools that have markedly improved the diagnostic rate of GI diseases, there are still some limitations, including instability of human diagnostic performance caused by intensive labor burden and high missed diagnosis rate of subtle lesions. Recently, artificial intelligence (AI) has been applied gradually to assist endoscopists in addressing these issues.

Methods and Results:

In this study, we provide an overview of the application of the AI technology in the field of endoscopy, as well as its current limitations and prospects. The result suggested that AI had a significantly higher diagnostic accuracy compared with human endoscopists in the diagnosis of GI diseases. With the help of AI technology, the diagnostic performances of nonexpert endoscopists had been improved considerably.

Conclusion:

AI technology still has several limitations, and there are still plenty of opportunities for improvement.
Treatment Approach Considerations for Children With Speech Sound Disorders in School-Based Settings
Authors: Cabbage Kathryn L. , DeVeney Shari L.
Published: October 2020

Clinicians providing intervention for pediatric speech sound disorders (SSDs) have many treatment approach options from which to select. Because treatment needs vary across children based on many factors including the error type(s) present and patterns of deficit noted, these factors need to be considered early in the therapeutic process to find the best-suited approach. In this article, the authors describe and contrast a traditional motor articulatory-based approach with phonologically-based approaches including cycles, contrast therapies (e.g., minimal pairs, maximal oppositions, and multiple oppositions), and complexity through presentation of hypothetical case studies, updated summaries of the evidence base for each, and a summary of current research limitations for informing clinical practice. Although children with SSDs are ubiquitous in pediatric clinical caseloads, familiarity or lack thereof with the evidence base supporting different approaches potentially limits speech production outcomes for children receiving speech services. Even so, limitations in the evidence base constrain practical application of a given approach to daily therapeutic interactions.
Real world hypertension treatment patterns analysis identifies putative gaps and risk-associated patterns
Authors: Bandhakavi Sricharan , McCammon Jasmine M. , Karigowde Sunil , Liu Zhipeng , Ni Xianglian , Rahmanian Farbod
Published: October 2020

Objective

Although treatment patterns’ analyses at scale can provide insights into associated health outcomes, they remain relatively uncharacterized for most chronic diseases, including hypertension (HTN). To address this gap, we analyzed HTN treatment patterns among US health-insured patients.

Materials and Methods

New (n = 200,786) or all (n = 4.1 million) HTN patients were identified from 2015, 2016 enrollments in a nationwide administrative claims’ database and compared for HTN-specific treatment (Rx) choices, Rx count, and distinct roundsof treatmentoptions (ROTO), respectively. Selected treatment patterns were risk-assessed using predictive modeling and/or literature-based recommendations.

Results

For 2016, ACE inhibitors/ARBs were most frequent choices in new HTN patients’ vs more diverse Rx-choices among all HTN patients. All HTN patients had ∼3-fold and ∼5-fold-higher prevalence of (same-year) polytherapy and Rx interventions, respectively.

New HTN patients with ≥2 rounds of treatment options (vs single/initial round) were associated with ∼5-fold or higher predicted HTN complications’ risk (p-value < 0.0001). All HTN patients with ≥3 rounds of treatment options (vs single/initial round) had 3.8-fold higher next-year HTN complications’ risk (p-value < 0.0001). Co-morbidities/persistence of ≥3 rounds of treatment options over 2 years further increased these odds and total medications/chronic disease score correlated with ROTO counts.

Discussion

∼95% of new HTN patients in 2016 did not start treatment with current literature-recommended first option, Thiazides. Assuming “sticky” prescription patterns, opportunity exists to improve (current) initial HTN treatments. Additionally, ROTO counts can inform HTN complications’ risk/management thereof.

Conclusion

We highlight opportunities to improve initial HTN treatments and treatment patterns associated with higher risk among HTN patients.
Durable SARS-CoV-2 B cell immunity after mild or severe disease
Authors: Ogega Clinton O. , Skinner Nicole E. , Blair Paul W. , Park Han-Sol , Littlefield Kirsten , Ganesan Abhinaya , Ladiwala Pranay , Antar Annukka AR , Ray Stuart C. , Betenbaugh Michael J. , Pekosz Andrew , Klein Sabra L. , Manabe Yukari C. , Cox Andrea L. , Bailey Justin R.
Published: October 2020

Multiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease, and hospitalized patients with moderate to severe disease, at a median of 54 (39-104) days after onset of symptoms. We detected S-RBD-specific class-switched MBC in 13 out of 14 participants, including 4 of the 5 participants with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific class-switched MBC in both cohorts. FCRL5, a marker of functional memory when expressed on rMBC, was dramatically upregulated on S-RBD-specific rMBC. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched MBC that phenotypically resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after recovery from mild or severe COVID-19 disease.

Graphical Abstract
Predicting the Disposition of the Antimalarial Drug Artesunate and its Active Metabolite Dihydroartemisinin Using Physiologically-Based Pharmacokinetic Modeling
Authors: Arey Ryan , Reisfeld Brad
Published: October 2020

Artemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required, and one approach to predict these pharmacokinetic characteristics is physiologically-based pharmacokinetic (PBPK) modeling. In this study, a whole-body PBPK model was developed to simulate the time-dependent tissue concentrations of artesunate (AS) and its active metabolite, dihydroartemisinin (DHA). The model was developed for both rats and humans and incorporated drug metabolism of the parent compound and major metabolite. Model calibration was conducted using data from the literature in a Bayesian framework, and model verification was assessed using separate sets of data. Results showed good agreement between model predictions and the validation data, demonstrating the capability of the model in predicting the blood, plasma, and tissue pharmacokinetics of AS and DHA. It is expected that such a tool will be useful in characterizing the disposition of these chemicals and ultimately improve dosing regimens by enabling a quantitative assessment of the tissue-specific drug levels critical in the evaluation of efficacy and toxicity.