bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the day-time ground-level turbulence at Mt Wumingshan with a microthermal sensor
Authors: Song Tengfei , Liu Yu , Cai Zhanchuan , Zhao Mingyu , Zhang Xuefei , Wang Jingxing , Li Xiaobo , Huang Shanjie , Song Qiwu , Du Zhimao
Published: May 2021

Surface-layer turbulence, especially the turbulence close to the ground (ground-level, GL), critically determines the height at which to locate a ground-based telescope. It is also vital to assess the contribution of the GL to the total turbulence. To characterize the day-time turbulence at the GL at the Mt Wumingshan (Mt WMS) site (a candidate site for the Chinese next-generation large Solar Telescope), a microthermal sensor (MS) was installed to detect fluctuations of the temperature at the GL and estimate the contribution of the GL to the total turbulence. The MSs were placed at six levels on a 22-m-high tower to measure the refractive index $C_{n}^{2}$ configuration constant. This study presents the day-time optical turbulences due to the GL at the Mt WMS site and compares them with the integrated day-time seeing that was obtained by the Wumingshan Mountain Automated Solar Differential Image Motion Monitor (WMA-SDIMM). MS and WMA-SDIMM data were obtained simultaneously for a total of 16 d during June to October 2017. The average r0 of the GL was found to be $r_{0}^{\rm gl}(\rm {1\, m,16\, m})=11.04\, {\rm cm}$ and $r_{0}^{\rm gl}({\rm 16\,m,22\,m})=61.64\,{\rm cm}$. The contribution of the GL (8 to 22 m) to the total turbulence was $13.05{{\ \rm per\ cent}}$ on average, complying with a $8.0{{\ \rm per\ cent}}$ reduction of the total seeing. At the height of 22 m, most of the GL turbulence was produced below 16 m.
Differentiating modern and prebiotic Earth scenarios for TRAPPIST-1e: high-resolution transmission spectra and predictions for JWST
Authors: Lin Zifan , MacDonald Ryan J , Kaltenegger Lisa , Wilson David J
Published: May 2021

The TRAPPIST-1 system is a priority target for terrestrial exoplanet characterization. TRAPPIST-1e, residing in the habitable zone, will be observed during the James Webb Space Telescope (JWST) GTO Program. Here, we assess the prospects of differentiating between prebiotic and modern Earth scenarios for TRAPPIST-1e via transmission spectroscopy. Using updated TRAPPIST-1 stellar models from the Mega-MUSCLES survey, we compute self-consistent model atmospheres for a 1 bar prebiotic Earth scenario and two modern Earth scenarios (1 and 0.5 bar eroded atmosphere). Our modern and prebiotic high-resolution transmission spectra ($0.4\!-\! 20\, \rm{\mu m}$ at R ∼100 000) are made available online. We conduct a Bayesian atmospheric retrieval analysis to ascertain the molecular detectability, abundance measurements, and temperature constraints achievable for both scenarios with JWST. We demonstrate that JWST can differentiate between our prebiotic and modern Earth scenarios within 20 NIRSpec Prism transits via CH4 abundance measurements. However, JWST will struggle to detect O3 for our modern Earth scenario to $\gt 2\, \sigma$ confidence within the nominal mission lifetime (∼ 80 transits over 5 yr). The agnostic combination of N2O and/or O3 offers better prospects, with a predicted detection significance of $2.7\, \sigma$ with 100 Prism transits. We show that combining MIRI LRS transits with Prism data provides little improvement to atmospheric constraints compared to observing additional Prism transits. Though biosignatures will be challenging to detect for TRAPPIST-1e with JWST, the abundances for several important molecules – CO2, CH4, and H2O – can be measured to a precision of ≲ 0.7 dex (a factor of 5) within a 20 Prism transit JWST program.
Direct transformation of n-alkane into all-trans conjugated polyene via cascade dehydrogenation
Authors: Li Xuechao , Niu Kaifeng , Zhang Junjie , Yu Xiaojuan , Zhang Haiming , Wang Yuemin , Guo Qing , Wang Pengdong , Li Fangsen , Hao Zhengming , Xu Chaojie , Tang Yanning , Xu Zhichao , Lu Shuai , Liu Peng , Xue Guigu , Wei Yen , Chi Lifeng
Published: May 2021

Selective C(sp3) −H activation is of fundamental importance in processing alkane feedstocks to produce high-value-added chemical products. By virtue of an on-surface synthesis strategy, we report selective cascade dehydrogenation of n-alkane molecules under surface constraints, which yields monodispersed all-trans conjugated polyenes with unprecedented length controllability. We are also able to demonstrate the generality of this concept for alkyl-substituted molecules with programmable lengths and diverse functionalities, and more importantly its promising potential in molecular wiring.
Management of Mobile Thrombus With Distal Protection Devices During Carotid Artery Angioplasty: 2-Dimensional Operative Video
Authors: Cohen-Cohen Salomon , Lanzino Giuseppe , Brinjikji Waleed ,   Endovascular Neurosurgery Research Group (ENRG), Arthur Adam , Bain Mark , Bendock Bernard , Binning Mandy Jo , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad I , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan H , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: May 2021

Embolic protection devices (EPDs) have become a standard of care during internal carotid artery revascularization.
1,2
This video is about a 57-yr-old-male who presented with a wake-up stroke with a left hemispheric syndrome. Head computed tomography angiography (CTA) revealed tandem occlusions of the proximal left internal carotid artery (ICA) and of the distal left middle cerebral artery (MCA) with an ASPECT (Alberta Stroke Program Early CT Score) score of 6. The patient underwent a cerebral angiogram and was treated with balloon angioplasty with a distal EPD and mechanical thrombectomy. The EPD became occluded with thrombus from the ICA and was retrieved through a 6-Fr Sofia (MicroVention) under continuous aspiration. Successful revascularization of the proximal ICA and distal MCA was achieved. No procedure-related complications occurred, and the patient's neurological exam improved. Tandem occlusions can occur in up to 15% of strokes. The optimal treatment can be controversial, but mechanical thrombectomy and ICA revascularization with a distal EPD appear to be safe and effective in selected patients.
3
Consent was obtained for the procedure and for the video production.
Hearing Preservation Surgery in the Sitting Position for Grade 3B Hannover Classification Vestibular Schwannoma: 3-Dimensional Operative Video
Authors: O’Donnell Devon , Dehdashti Amir R
Published: May 2021

Surgical treatment of large vestibular schwannomas is challenging. Both facial and cochlear nerves should be preserved in patients who have no neurological deficit preoperatively. In this 3-dimensional video, we present a 35-yr-old patient who presented with documented increase in the size of a known vestibular schwannoma over the span of 3 yr. Surgery was favored among all treatment options due to his young age and the tumor size. Informed consent was obtained. Semisitting surgery allowed for bimanual microdissection of the tumor capsule from the surrounding arachnoid and cranial nerves with 2 micro dissectors. The precision of microdissection is enhanced in the sitting position. Facial nerve stimulation remained stable at 0.05 mA. The auditory evoked potential remained unchanged during the surgery. Complete resection of the tumor and preservation of facial and cochlear nerves was achieved. The patient had a stable hearing grade B and a normal facial nerve function at 3-mo follow-up.
Entrepreneur Death and Startup Performance
Authors: Becker Sascha O , Hvide Hans K
Published: May 2021

How large is entrepreneurs’ personal importance to startups? We use the death of nearly 1,500 entrepreneurs as a source of exogenous variation, and find large and sustained negative effects on growth and profitability. For small startups, the effects go mainly via firm survival, while for larger startups the effects are mainly on firm growth. For larger startups, the mean effect on sales is about 60%. The effects appear to be driven by entrepreneur specialness rather than leadership transition; the effects of death of entrepreneur managers are economically and statistically stronger than the death of managers that are not entrepreneurs.
Infectivity of patent Plasmodium falciparum gametocyte carriers to mosquitoes: establishing capacity to investigate the infectious reservoir of malaria in a low-transmission setting in The Gambia
Authors: Ahmad Abdullahi , Soumare Harouna M , Camara Muhammed M , Jadama Lamin , Gaye Pa Modou , Bittaye Haddy , Bradley John , Achan Jane , Bousema Teun , D'Alessandro Umberto , Drakeley Chris , Moreno Marta
Published: May 2021

Background

Understanding the human malaria infectious reservoir is important for elimination initiatives. Here, we implemented mosquito membrane feeding experiments to prepare for larger studies to quantify the transmission potential and relative contribution of the human infectious reservoir.

Methods

Patients with clinical malaria attending four health facilities with at least 16 Plasmodium falciparum gametocytes per μL were recruited during the 2018 transmission season. Infectiousness to mosquitoes was assessed by direct membrane feeding assay (DMFA). We compared our results with a Bayesian predictive model to investigate the relationship between infectiousness and gametocyte density and explore the impact of fever on gametocyte infectivity.

Results

A total of 3177 suspected malaria cases were screened; 43.3% (1376) had microscopically patent P. falciparum parasites and 3.6% (114) of them had gametocytes. Out of 68 DMFAs, 38 (55.9%) resulted in at least one infected mosquito, with a total of 15.4% (1178/7667) of mosquitoes infected with 1–475 oocysts per gut. The relationship between mosquito infection prevalence and gametocytaemia was similar to other African settings and negatively associated with fever (OR: 0.188, 95% CI 0.0603 to 0.585, p=0.0039).

Conclusions

Among symptomatic malaria patients, fever is strongly associated with transmission failure. Future studies can use DMFA to better understand the human malaria reservoir in settings of low endemicity in The Gambia and inform malaria elimination initiatives.
Spatiotemporal Quantification of Plasmodiophora brassicae Inoculum in Relation to Clubroot Development Under Inoculated and Naturally Infested Field Conditions
Authors: Xing Manzhu , Guan Gege , Zhang Xinyu , Sun Huiying , Wang Zehao , Pang Wenxing , Piao Zhongyun , Yang Xinyu , Feng Jie , Liang Yue
Published: May 2021

Clubroot caused by Plasmodiophora brassicae is a destructive disease of cruciferous plants worldwide. A quantitative PCR (qPCR) system specific to P. brassicae was developed. Analysis of the qPCR sensitivity indicated that the lower limit of detection was 1 × 101 resting spores/ml, 1 × 102 spores/g of soil, and 1 × 103 spores/g of roots and seeds. The regression curves generated from the qPCR data of different samples had a parallel relationship. The difference between the theoretical and actual concentrations was lowest at 1 × 105 spores/g of sample, compared with other concentrations. The P. brassicae biomass in soil and plant root tissues after inoculated with different spore concentrations was correlated. A correlation analysis confirmed that the clubroot incidence and disease index at 6 weeks after inoculation increased as the spore concentration increased. Under field conditions, the natural inoculum density of the P. brassicae population decreased at the early stage and then increased, with P. brassicae mainly being detected at a soil depth of 0 to 50 cm. The horizontal distribution of P. brassicae varied in the field with occurrences of hot spots. This study established a qPCR-based method for quantitative detection of clubroot. The developed assay is useful for monitoring the spatiotemporal dynamics of P. brassicae in the field. It may also be applicable for clubroot forecasting as a part of proactive disease management.
Chiral Pharmacokinetics and Metabolite Profile of Prolonged-release Ketamine Tablets in Healthy Human Subjects
Authors: Hasan Mahmoud , Modess Christiane , Roustom Tarek , Dokter Anne , Grube Markus , Link Andreas , Rey Hélène , Adler Stefanie , Meissner Konrad , Siegmund Werner
Published: May 2021

Background

The anesthetic ketamine after intravenous dosing is nearly completely metabolized to R- and S-stereoisomers of the active norketamine (analgesic, psychoactive) and 2,6-hydroxynorketamine (potential analgesic, antidepressant) as well as the inactive dehydronorketamine. Oral administration favors the formation of 2,6-hydroxynorketamines via extensive presystemic metabolism. The authors hypothesized that plasma exposure to 2,6-hydroxynorketamines relative to the psychoactive ketamine is greater after prolonged-release ketamine tablets than it is after intravenous ketamine.

Methods

Pharmacokinetics of ketamine after intravenous infusion (5.0 mg) and single-dose administrations of 10, 20, 40, and 80 mg prolonged-released tablets were evaluated in 15 healthy white human subjects by means of a controlled, ascending-dose study. The stereoisomers of ketamine and metabolites were quantified in serum and urine by validated tandem mass-spectrometric assays and evaluated by noncompartmental pharmacokinetic analysis.

Results

After 40 mg prolonged-release tablets, the mean ± SD area under the concentrations–time curve ratios for 2,6-hydroxynorketamine/ketamine were 18 ± 11 (S-stereoisomers) and 30 ± 16 (R-stereoisomers) compared to 1.7 ± 0.8 and 3.1 ± 1.4 and after intravenous infusion (both P < 0.001). After 10 and 20 mg tablets, the R-ratios were even greater. The distribution volumes at steady state of S- and R-ketamine were 6.6 ± 2.2 and 5.6 ± 2.1 l/kg, terminal half-lives 5.2 ± 3.4 and 6.1 ± 3.1 h, and metabolic clearances 1,620 ± 380 and 1,530 ± 380 ml/min, respectively. Bioavailability of the 40 mg tablets was 15 ± 8 (S-isomer) and 19 ± 10% (R-isomer) and terminal half-life 11 ± 4 and 10 ± 4 h. About 7% of the dose was renally excreted as S-stereoisomers and 17% as R-stereoisomers.

Conclusions

Prolonged-release ketamine tablets generate a high systemic exposure to 2,6-hydroxynorketamines and might therefore be an efficient and safer pharmaceutical dosage form for treatment of patients with chronic neuropathic pain compared to intravenous infusion.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Rituximab Treatment for Chronic Idiopathic Axonal Polyneuropathy
Authors: Moussa Hussein , Sawaya Raja A.
Published: May 2021

Chronic idiopathic axonal polyneuropathy is a disorder of unknown etiology resulting in progressive weakness and sensory disturbances predominantly in the hands and feet. Nerve conduction studies and electromyography confirm axonal damage in the nerves of the upper and lower extremities. The pathology is symmetrical with a distal predilection. Patients usually do not respond to the classical treatment with steroids, intravenous immunoglobulin, plasmapheresis, or immunosuppressant drugs. We describe 2 cases of chronic idiopathic axonal polyneuropathy who received intravenous rituximab as a last resort because of the severity of their symptoms. Both patients showed dramatic improvement in their weakness, muscle atrophy, numbness, and paresthesias only few weeks after the induction dose. Their daily functional activities improved to self-independence.
Clinical Features and Treatment Response in Immune-Mediated Small Fiber Neuropathy with Trisulfated Heparin Disaccharide or Fibroblast Growth Factor Receptor 3 Antibodies
Authors: Zeidman Lawrence A. , Kubicki Konrad
Published: May 2021

Objective:

Novel antibodies to trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) have been recently described in otherwise cryptogenic small fiber neuropathy (SFN) cases. Our goal was to further describe clinical features in such cases and to analyze treatment responses.

Methods:

In a retrospective analysis, 40 cases of cryptogenic SFN in a university neuropathy clinic were identified. Of these, TS-HDS and FGFR-3 cases were identified, and clinical features and treatment responses were analyzed.

Results:

In this cohort, 95% were women, and 55% had either TS-HDS or FGFR-3 antibodies (77% of these had TS-HDS). Of the seropositive group, 41% had a nonlength dependent epidermal nerve fiber density on skin punch biopsy (OR = 1.80). In the seropositive group, 82% had neuropathic pain as their primary symptom (OR = 1.73). Also 32% of seropositive patients reported widespread pain (OR = 1.63). 63% of seropositive cases presented acutely (OR = 11.0). In the seropositive group, 23% had an initial erroneous diagnosis (OR = 1.47). Eight seropositive patients improved on intravenous immunoglobulin treatment, with a 42% reduction in pain scores (P = 0.02), a 44% reduction in the Utah Neuropathy Score, and improved epidermal nerve fiber density post-treatment.

Conclusions:

TS-HDS and FGFR-3 antibodies may be present in a high proportion of cryptogenic SFN cases with acute onset, nonlength dependent pathology, and primary neuropathic and widespread pain. They are often misdiagnosed as other conditions including fibromyalgia. These cases may be responsive to immune treatment, especially with intravenous immunoglobulin.
What is in the Literature
Authors: Bromberg Mark B.
Published: May 2021

This edition of What is in the Literature focuses on chronic immune neuropathies as they represent treatable conditions. There are formal criteria to solidify the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but patients are encountered who have clinical and electrodiagnostic features of CIDP but do not fulfill diagnostic criteria. These patients are addressed in recent publications. CIDP (and variants) and other forms of immune-mediated neuropathies (multifocal motor neuropathy) are responsive early on to treatment, but long-term factors are less well described, and a number of publications focus on extended consequences. Acute immune neuropathies have been described in the setting of viral illness, and recent publications look at the question as to whether they are associated with the COVID-19 pandemic. Finally, idiopathic sensory neuropathies are the most common polyneuropathy, and consensus efforts to codify features into subtypes can be used clinically for a more precise diagnosis.
Hsp90 Inhibitor Attenuates the Development of Pathophysiological Cardiac Fibrosis in Mouse Hypertrophy via Suppression of the Calcineurin-NFAT and c-Raf-Erk Pathways
Authors: Marunouchi Tetsuro , Nakashima Miyuki , Ebitani Saika , Umezu Sakiko , Karasawa Kasane , Yano Emi , Tanonaka Kouichi
Published: May 2021

In the previous study, we showed that an Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), attenuates hypertrophic remodeling of cardiomyocytes during the development of heart failure. In this present study, we investigated the effects of 17-AAG on cardiac fibrosis during the development of heart failure. We used pressure-loaded cardiac hypertrophic mice prepared by constriction of the transverse aorta (TAC), which induces significant cardiac fibrosis without scar tissue. From the sixth week after the TAC operation, vehicle or 17-AAG was administered intraperitoneally twice a week. Eight weeks after the operation, the vehicle-treated animals showed chronic heart failure. On the other hand, cardiac deterioration of the 17-AAG–treated animals was attenuated. In 17-AAG–treated animals, when the degree of fibrosis was observed by histological staining, their volume of fibrosis was found to be reduced. The content of calcineurin, an Hsp90 client protein, and the level of dephosphorylated NFATc2, a transcription factor in the cardiac fibroblasts, in the TAC mice was reduced by treatment with 17-AAG. Furthermore, c-Raf and Erk signaling, indicators for cell proliferation and collagen synthesis, was also attenuated. In in vitro experiments, the proliferation and collagen synthesis of the cultured cardiac fibroblasts were attenuated by the presence of 17-AAG. When cardiac fibroblasts were incubated with angiotensin II, calcineurin–NFATc2 and c-Raf–Erk signaling in the cells were activated. These activations were attenuated by 17-AAG. Our findings suggest that suppression of the calcineurin–NFAT and c-Raf–Erk pathways may partially contribute to the attenuation of myocardial fibrosis caused by treatment with 17-AAG. Therefore, our data imply that the Hsp90 inhibitor may have potential for novel therapeutic strategy for the treatment of heart failure.
Evaluating Surgical Decision-making in Nonsyndromic Sagittal Craniosynostosis Using a Digital 3D Model
Authors: Hughes Christopher D. , Langa Olivia , Nuzzi Laura , Staffa Steven J. , Proctor Mark , Meara John G. , Ganske Ingrid M.
Published: May 2021

Background:

Surgical correction of craniosynostosis addresses potentially elevated intracranial pressure and the cranial deformity. In nonsyndromic sagittal synostosis, approximately 15% of patients have elevated intracranial pressure. The decision to operate therefore likely reflects a combination of aesthetic goals, prevention of brain growth restriction over time, surgeon training and experience, and parental expectations. This study examines clinical factors that influence surgical decision-making in nonsyndromic sagittal synostosis.

Methods:

An online survey sent to craniofacial and neurosurgeons presented 5 theoretical patients with varying severities of sagittal synostosis. For each cephalic index, 4 separate clinical scenarios were presented to assess influences of parental concern and developmental delay on the decision to operate.

Results:

Fifty-six surveys were completed (response rate = 28%). Participants were predominantly from North America (57%), had over 10 years of experience (75%), and performed over 20 craniosynostosis procedures annually (50%). Thirty percent of respondents indicated they would operate regardless of head shape and without clinical and/or parental concern. Head shape was the greatest predictor of decision to operate (P < 0.001). Parental concern and developmental delay were independently associated with decision to operate (P < 0.001). Surgeons with more experience were also more likely to operate across all phenotypes (OR: 2.69, P < 0.004).

Conclusions:

Surgeons responding to this survey were more strongly compelled to operate on children with nonsyndromic sagittal craniosynostosis when head shape was more severe. Additional factors, including parental concern and developmental delay, also influence the decision to operate, especially for moderate phenotypes. Geographic and subspecialty variations were not significant.
Arteriovenous Fistula Rescues Radial Forearm Phalloplasty: A Case Report on Patients with Microvascular Obstruction
Authors: Santucci Richard A. , Newsom Keeley D. , Wachtman Galen S. , Crane Curtis N.
Published: May 2021

Background:

Radial forearm free flap phalloplasty (RFFFP) is the most common surgery performed for genital reconstruction of female-to-male transgender patients. However, up to 19% require anastomotic re-exploration. The postoperative creation of an arteriovenous fistula (AVF) to bypass obstruction and salvage RFFFP was first reported in 1996 and has subsequently been reported by 1 high-volume center in Belgium.

Methods:

Here, we present 2 cases in which intraoperative microvascular obstruction threatened the viability of the RFFF of transgender phalloplasty patients. In each patient, an AVF was created between the radial artery and cephalic vein in the distal flap either after being transferred out of the operating room, as has previously been described, or during initial operation.

Results:

In both cases, the creation of a distal AVF salvaged the neophallus. Importantly, the patient that had been transferred out of the operating room before reintervention suffered partial flap necrosis compared with no flap loss in the patient who had an AVF created during initial surgery. One AVF was ligated 18 days postoperative, whereas the other was never formally closed.

Conclusions:

These cases demonstrate that AVF can be reliably used for RFFFP salvage both intraoperatively and for reintervention. They also suggest that earlier detection of persistent vascular compromise and utilization of AVF can further minimize flap loss. Finally, in contrast with the prior explanation of this technique, timing of AVF ligation may be less critical than previously described. Microsurgeons are reminded that this technique may save complicated flaps in the uncommon case of microcirculatory flap obstruction.
The Effect of Clinicians' Personal Acquaintance on Specialty Care Coordination as the Sharing of an EHR Increases
Authors: Vimalananda Varsha G. , Wormwood Jolie B. , Qian Shirley , Meterko Mark , Sitter Kailyn E. , Fincke B. Graeme
Published: May 2021

We used an online survey to measure how personal acquaintance with referring primary care providers (PCPs) affects specialists' experience of care coordination as use of a shared electronic health record (EHR) increases. Only 9% of specialists rated Overall Coordination as 9 or 10 out of 10. Personal acquaintance positively impacted Overall Coordination and all measured coordination subdomains. This effect was attenuated, but persisted, even at higher levels of EHR sharing. The impact of a shared EHR alone was limited to Overall Coordination and the Data Transfer subdomains. Health systems can improve coordination through investment in clinician relationships, while research should address the gaps in coordination even with widespread personal acquaintance and shared EHRs.
Defining Access Management in Health Care Delivery Organizations
Authors: Hempel Susanne , Hilton Lara G. , Stockdale Susan , Kaboli Peter , Miake-Lye Isomi , Danz Margie , Rose Danielle , Kirsh Susan , Curtis Idamay , Rubenstein Lisa V.
Published: May 2021

Managing patient access to care in health care delivery organizations is instrumental in shaping patient experiences. We convened an inclusive stakeholder panel, informed by evidence, to understand the dimensions and establish definitions of access and access management. The literature varies in access definitions, but the temporal measure “time to third next available appointment” was consistently used as an indicator of access. Panel deliberations highlighted the importance of patient-centeredness and resulted in comprehensive definitions for access management, optimal access management, and optimal access. Health care organizations and researchers can use the developed definitions and concepts as starting points for initiatives to improve access management.
Supporting “Bleeders” and “Billers”
Authors: Martinez-Hollingsworth Adrienne , Kim Linda , Richardson Tabia Graham , Angulo Marco , Liu Roger , Friedman Theodore , Choi Kristen
Published: May 2021

Organizational factors impacting burnout have been underexplored among providers in low-income, minority-serving, safety-net settings. Our team interviewed 14 health care administrators, serving as key decision makers in Federally Qualified Health Center primary care clinics. Using a semistructured interview guide, we explored burnout mitigation strategies and elements of organizational culture and practice. Transcribed interviews were coded and analyzed using the Braun and Clark (2006) Thematic Analysis method. Mission-Driven Ethos to Mitigate Provider Burnout emerged as the primary theme with 2 categories: (1) Promoting the Mission: “Bleeders” and (2) Competing Priorities: “Billers.” These categories represent various properties and reflect administrators' use of organizational mission statement as a driver of staff recruitment, training, retention, and stratification. Data collection occurred before and during the COVID-19 global pandemic, as such additional themes associated with administrative behaviors during a prolonged, clinical crisis provide insight into possible strategies that may mitigate burnout in this setting.
Proposed Framework for Considering SARS-CoV-2 Antigen Testing of Unexposed Asymptomatic Workers in Selected Workplaces
Authors: Schulte Paul A. , Piacentino John D. , Weissman David N. , de Perio Marie A. , Chiu Sophia K. , Radonovich Lewis J. , Trout Douglas , Beezhold Don , Hearl Frank J. , Howard John
Published: May 2021

Objectives:

To propose a framework for considering SARS-CoV-2 antigen testing of unexposed asymptomatic workers in selected workplaces.

Methods:

This is a commentary based on established occupational safety and health principles, published articles, and other pertinent literature, including non–peer-reviewed preprints in medrixiv.org prior to April 16, 2021.

Results:

Not applicable to this commentary/viewpoint article.

Conclusion:

Antigen testing is a rapidly evolving and useful public health tool that can be used to guide measures to reduce spread of SARS-CoV-2 in the community and in selected workplaces. This commentary provides a proposed framework for occupational safety and health practitioners and employers for considering antigen testing as a method to screen asymptomatic workers in selected non-healthcare settings. When applied selectively, antigen testing can be a useful, effective part of a comprehensive workplace program for COVID-19 prevention and control.
Localized hair loss in infancy: a review
Authors: McKenzie Paige L. , Castelo-Soccio Leslie
Published: May 2021

Purpose of review

The current review will address the different causes of localized hair loss in infancy. The data presented here will provide clinicians with the latest understanding of different disorders leading to localized hair loss and will provide recommendations for further management of infants who present with alopecia.

Recent findings

Localized hair loss in infancy is common, but its underlying causes vary greatly. Alopecia in infants can be categorized into congenital, genetic, inflammatory, mechanical, and physiologic causes. Decisions regarding further management are complex, as they often involve not only cosmetic concerns, but also work-up of possible systemic medical issues related to hair loss.

Clinicians must be able to distinguish between the different causes of infantile hair loss so that appropriate work-up and further management can be pursued. Factors such as physical appearance, timing of presentation, dermoscopic exam, histopathology, and associated systemic features can help lead clinicians to the correct diagnosis in the case of an infant with localized alopecia.
Caenorhabditis elegans as a Diagnostic Aid for Pancreatic Cancer
Authors: Kobayashi Masanori , Fujita Akashi , Ogawa Tomoya , Tanisaka Yuki , Mizuide Masafumi , Kondo Nobuaki , Imaizumi Yuki , Hirotsu Takaaki , Ryozawa Shomei
Published: May 2021

Objectives

Early detection of pancreatic cancer is notoriously difficult. A novel cancer diagnostic method using the ability of nematodes to detect odor of urine samples has been developed (N-NOSE). This method has a high sensitivity and specificity for various cancers; however, it has not yet been verified in pancreatic cancer. We examined the usefulness of this method to aid early diagnosis of pancreatic cancer in a cancer center.

Methods

We collected urine samples and clinical data from patients hospitalized in our division, between July 2017 and February 2019. We excluded patients with a known current or past history of other cancers. We investigated the relationship between the results of N-NOSE and the presence of pancreatic cancer.

Results

There were 95 noncancer cases and 104 pancreatic cancer cases. The sensitivity and specificity of N-NOSE for pancreatic cancer were 84.6% (88/104) and 60% (57/95), respectively. N-NOSE was able to detect stages 0 to I pancreatic cancer and had a higher correlation with early-stage pancreatic cancer than advanced stage.

Conclusions

N-NOSE has sufficient sensitivity and specificity for use in clinical practice, and it holds great potential as a diagnostic aid for pancreatic cancer, especially for early-stage pancreatic cancer.
Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer
Authors: Domínguez-Muñoz J. Enrique , de la Iglesia-García Daniel , Nieto-García Laura , Álvarez-Castro Ana , San Bruno-Ruz Alba , Monteserín-Ron Luz , López-Díaz Javier , Iglesias-García Julio
Published: May 2021

Objectives

Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer.

Methods

A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes.

Results

Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62–31.74) after biliopancreatic drainage compared with −1.92% (interquartile range, −4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage.

Conclusions

Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.
Liver Metastasis–Directed Ablative Radiotherapy in Pancreatic Cancer Offers Prolonged Time Off Systemic Therapy in Selected Patients
Authors: Lee Grace , Kim Daniel W. , Oladeru Oluwadamilola T. , Niemierko Andrzej , Gergelis Kimberly R. , Haddock Michael G. , Toesca Diego A. S. , Koong Amanda J. , Owen Dawn , Weekes Colin , Hong Theodore S. , Chang Daniel T. , Hallemeier Christopher L. , Wo Jennifer Y.
Published: May 2021

Objectives

We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)–directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis.

Methods

A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT.

Results

Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2–3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS.

Conclusions

Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.
Predictors of Poor Pathological Response to Neoadjuvant Gemcitabine Plus S-1 Chemotherapy in Patients With Pancreatic Ductal Adenocarcinoma
Authors: Mori Shozo , Aoki Taku , Sakuraoka Yuhki , Shimizu Takayuki , Yamaguchi Takamune , Park Kyung-Hwa , Matsumoto Takatsugu , Shiraki Takayuki , Iso Yukihiro , Kubota Keiichi
Published: May 2021

Objectives

Although neoadjuvant chemotherapy (NAC)–gemcitabine plus S-1 (GS) has been reported to have a survival benefit in patients with resectable pancreatic ductal adenocarcinoma (PDAC), optimal candidates for NAC-GS have not been clearly identified.

Methods

A total of 81 patients with PDAC who underwent pancreatectomy after NAC-GS between 2013 and 2019 were divided into 2 groups based on Evans classification: grade I (<10% tumor cell destruction, n = 19) and grades II and III (>10% tumor cell destruction, n = 62). Univariate and multivariate analyses using clinical characteristics available before initiation of NAC were performed to predict Evans classification grade I (Evans I).

Results

The overall survival in patients with Evans I was significantly lower than that in patients with Evans II and III (P < 0.001). Multivariate analysis revealed a carcinoembryonic antigen level of >3.6 ng/mL (P = 0.001) and C-reactive protein to albumin ratio of >0.062 (P = 0.017) as independent predictors for Evans I disease. Seven of 11 patients who met both criteria had Evans I disease.

Conclusions

Serum carcinoembryonic antigen and C-reactive protein to albumin ratio are associated with Evans I disease in patients with PDAC who receive NAC-GS. Patients who meet both predictors may not be optimal candidates for NAC-GS.
Thromboembolic Complications in the First Year After Acute Pancreatitis Diagnosis
Authors: Robbins Alexandria J. , Lusczek Elizabeth , Bellin Melena D. , Benner Ashley , Alwan Fatima S. , Beilman Gregory J.
Published: May 2021

Objectives

This study aimed to quantify the prevalence of venous thromboembolic (VTE) events in patients with pancreatitis requiring hospitalization and its impact on outcomes.

Methods

Adult patients admitted from 2011 to 2018 for pancreatitis were identified. Every admission for pancreatitis in the first year after diagnosis was evaluated for a VTE (pulmonary embolism, deep vein thrombosis, or mesenteric vessel thrombosis) within 30 days of discharge. Characteristics of patients who developed a thromboembolic event were compared with those who did not.

Results

There were 4613 patients with pancreatitis identified, 301 of whom developed a VTE (6.5%). Patients who developed a VTE were more likely to be male (P < 0.01), older (P = 0.03), and have an underlying coagulopathy (P < 0.01). Those with VTEs were more likely to die (27% vs 13%, P < 0.01), have more readmissions for pancreatitis (1.7 vs 1.3, P < 0.01), longer length of stay (16 vs 5.5 days, P < 0.01), and be discharged to acute or long-term rehabilitation rather than home (P < 0.01).

Conclusions

Acute pancreatitis requiring hospitalization is associated with high risk of VTE in the first year after diagnosis. Thromboembolic disease is associated with worse morbidity and mortality.
Hypoxia Promotes Pancreatic Cancer Cell Dedifferentiation to Stem-Like Cell Phenotypes With High Tumorigenic Potential by the HIF-1α/Notch Signaling Pathway
Authors: Mu Rui , Zou Yong-Kang , Tu Kui , Wang Dian-Bei , Tang Dan , Yu Zhou , Zhao Lijin
Published: May 2021

Objectives

This study aimed to investigate the effect and mechanism of hypoxia on pancreatic cancer (PC) cell dedifferentiation and tumorigenic potential.

Methods

Inhibition of hypoxia-inducible factor 1α (HIF-1α) and overexpression of Notch1 in PC HS766T cell lines were by lentiviral transfection. The expression of stem cell-specific markers C-X-C motif chemokine receptor 4, CD44, and Nestin was detected by immunofluorescence and Western blot assays. Cell invasion capacity was examined by Transwell assay. Tumorigenic potential was measured in an in situ tumor transplantation experiment. The expression of HIF-1α, Notch signals, and apoptosis signals was examined by Western blot assay.

Results

Hypoxia promoted PC cells to dedifferentiate into stem-like cells by upregulating HIF-1α and activating Notch signals. Silencing of HIF-1α significantly repressed cell dedifferentiation and invasion, whereas overexpression of Notch1 reversed the effect of HIF-1α repression. In situ tumor transplantation experiment further confirmed that hypoxia promoted tumorigenic ability through upregulating HIF-1α. Moreover, the expression of HIF-1α and Notch1 was significantly increased in human PC tissues, and high expression of HIF-1α was correlated with poor survival rate.

Conclusions

Hypoxia promoted PC cell dedifferentiation to stem-like cell phenotypes with high tumorigenic potential by activating HIF-1α/Notch signaling pathway, indicating a novel role in regulating PC progression.
Mutation Analysis and Disease Features at Presentation in a Multi‐Center Cohort of Children With Monogenic Cholestasis
Authors: Hertel Paula M. , Bull Laura N. , Thompson Richard J. , Goodrich Nathan P. , Ye Wen , Magee John C. , Squires Robert H. , Bass Lee M. , Heubi James E. , Kim Grace E. , Ranganathan Sarangarajan , Schwarz Kathleen B. , Bozic Molly A. , Horslen Simon P. , Clifton Matthew S. , Turmelle Yumirle P. , Suchy Frederick J. , Superina Riccardo A. , Wang Kasper S. , Loomes Kathleen M. , Kamath Binita M. , Sokol Ronald J. , Shneider Benjamin L. ,   Childhood Liver Disease Research Network (ChiLDReN)
Published: May 2021

Objectives:

To advance our understanding of monogenic forms of intrahepatic cholestasis.

Methods:

Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)‐binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)‐binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data.

Results:

Ninety‐eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including four monoallelic) deficiency were analyzed. Thirty‐five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported.

Conclusions:

In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype–phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.
Guidance for Beverages in the Diets of Children Younger Than 2 Years
Authors: Baker Susan S. , Bodnar Lisa M. , Benjamin‐Neelon Sara E.
Published: May 2021

Recently the National Academies of Sciences, Engineering, and Medicine reported a summary of recommendations from high‐income countries on what and how to feed infants and children from birth to 2 years of age. The report notes generally consistent recommendations against providing sugar‐sweetened beverages (SSB), juice, and beverages that contain nonnutritive sweeteners to infants and children younger than 2 years. When counselling parents and other caregivers, pediatricians should feel empowered to advise against offering these beverages.
Disparities in Telehealth Utilization Within Pediatric Gastroenterology
Authors: Puthenpura Vidya , Du Nan , Hauptman Leora , Porto Anthony F.
Published: May 2021

Objectives:

While the use of telemedicine has accelerated significantly with the recent pandemic, it has also magnified disparities in access to telemedicine. This study aims to look at telemedicine utilization patterns within a large pediatric gastroenterology practice.

Methods:

A retrospective study of ambulatory care visits within Yale‐New Haven Hospital's pediatric gastroenterology practice during the peak expansion of the telemedicine program was conducted. Zip code−level socioeconomic data were obtained using the Distressed Communities Index. A multivariate logistic regression to evaluate disparities between the use of video versus telephone visits was computed, and unadjusted and adjusted odds ratios with 95% confidence intervals (CIs) were obtained.

Results:

A total of 1273 clinic visits were included in analysis. The majority of the patients listed English as their preferred language, had private insurance, and identified as non‐Hispanic White. When adjusting for co‐variates, having public insurance/Medicaid was associated with decreased odds of having video over telephone visits (adjusted odds ratio [aOR] 0.60; 95% CI 0.44–0.80). Those whose primary language was not English continued to have a statistically significant decreased odds of using video visits (Spanish aOR 0.24; 95% CI 0.13–0.44; other aOR 0.29; 95% CI 0.12–0.72). Within the adjusted multivariate logistic regression, race/ethnicity and SES were, however, no longer found to have a statistically significant decreased odds of video visits.

Conclusions:

The accelerated implementation of telemedicine within pediatric gastroenterology has given rise to disparities in its use. Further studies are needed to understand these disparities and develop interventions to lessen this gap in usage.
Transient Elastography in Pediatric Liver Disease
Authors: Banc‐Husu Anna M. , Bass Lee M.
Published: May 2021

Transient elastography is an imaging technique utilizing shear wave technology to measure liver stiffness. Recent studies have shown success in utilizing this technique in children. Transient elastography is useful in estimating degree of fibrosis in various pediatric liver diseases, including biliary atresia, alpha‐1‐antitrypsin deficiency, Alagille syndrome, cystic fibrosis‐related liver disease, and non‐alcoholic steatohepatitis among others. Confounding factors, however, may affect elastography measurements, such as obesity, severe inflammation, nonfasting state, and hepatic congestion, and should be considered whenever interpreting these measurements. Future studies will correlate liver stiffness on transient elastography and severity of disease.