bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposed Changes to the 2021 Residency Application Process in the Wake of COVID-19
Authors: Gabrielson Andrew T. , Kohn Jaden R. , Sparks Hayley T. , Clifton Marisa M. , Kohn Taylor P. 
Published: May 2020

The COVID-19 pandemic has brought unique challenges to the delivery of undergraduate medical education, particularly for current third-year medical students who are preparing to apply to residency. In mid-March, medical schools suspended all clinical rotations for the remainder of the 2019–2020 academic year. As such, third-year medical students may not be able to complete sufficient clinical experiences to make important career choices before they have to submit their residency applications. While the decision to suspend clinical rotations was necessary to protect students, specialty organizations and residency programs must mitigate the deficits in students’ clinical education caused by the COVID-19 pandemic.
In this Perspective, the authors identify potential challenges for third-year medical students and advocate for solutions to improve the residency application process for students and programs. First, they propose delaying the date that programs can access applicant data through the Electronic Residency Application Service, thereby affording students more time to complete clinical experiences, solidify their specialty decision, and strengthen their residency application. Second, the authors recommend a restriction on the number of visiting rotations that students are expected to complete to allow for a more equitable distribution of these important experiences. Third, they suggest that program directors from each specialty agree on a maximum number of applications per applicant (based on historical data) to curb an upsurge in applications that may stem from the unique circumstances created by COVID-19 without causing applicants undue stress. Lastly, the authors advocate that residency programs develop infrastructure to conduct video-based interviews and engage students through virtual networking events.
Amidst the unique environment created by COVID-19, the authors urge governing bodies, specialty organizations, and residency programs to consider these recommendations to improve the efficiency and reduce the stress surrounding the 2021 Match.
Long‐term Use of Bisacodyl in Pediatric Functional Constipation Refractory to Conventional Therapy
Authors: Bonilla Silvana , Nurko Samuel , Rodriguez Leonel 
Published: May 2020

ABSTRACTObjectives:Standard therapy for pediatric constipation includes osmotic laxatives with stimulant laxatives use only as rescue therapy. Limited information is available on regular and long‐term use of bisacodyl in pediatric population despite its common use in adult and pediatric constipation.Methods:Retrospective review of patients with functional constipation refractory to conventional therapy (regular use of osmotic laxatives and intermittent use of stimulant laxatives only as a rescue therapy) referred to tertiary care children's hospital (January 2007–December 2014). Patients had a bowel movement (BM) frequency of ≤2 per week and were treated with bisacodyl regularly for longer than 4 weeks. Demographic variables, bisacodyl dose and treatment duration, number of BM/week before and after treatment, side effects, and length of follow‐up were recorded. Response to therapy was successful when frequency of BM increased from baseline to ≥3 BM/wk.Results:A total of 164 patients were included, 52% girls, median age 9.45 years (0.9–21 years). Bisacodyl median dose was 5 mg/day, median duration of treatment was 14 months (1–77 months) with 90% of patients taking the medication for <36 months. Median number of BM/wk doubled after initiation of bisacodyl from 2 to 4 bm/w (P < 0.001). Approximately 57% of patients had successful response. At long‐term follow‐up 55% of patients were successfully weaned off bisacodyl (median time of 18 months). Side effects reported in 9% of patients.Conclusions:Bisacodyl is effective and well tolerated in the long‐term treatment of pediatric functional constipation refractory to conventional therapy. Most of patients with a favorable response were successfully weaned off the medication.
Current cannabis-related situation in the Asia-Pacific region
Authors: Areesantichai Chitlada , Perngparn Usaneya , Pilley Catherine 
Published: May 2020

Purpose of review
We present information on cannabis policy, demand, and supply in the Asia-Pacific region.

Method
A systematic review of peer-reviewed articles using PubMed, MEDLINE, and reliable sources was conducted. We classified the policy implemented in each country into conducting research, legalization of medical and recreational use, decriminalization, cultivation, and others.

Recent findings
In Australia, New Zealand, and Thailand, medical use has been approved, whereas it is limited in South Korea and Singapore and illegal in other countries. Except Australia, none of the Asia-Pacific region countries allows recreational use. China and Japan are expected to approve medical use, whereas Australia and New Zealand work on decriminalization. Most cultivation is allowed and regulated for medical use. Cannabis seizures have changed in accordance with these policies. Although the national surveys of four countries, that is, Australia, New Zealand, Japan, and Thailand were conducted in different years, the use of cannabis among the general population has increased.

Summary
Any change in the legal status of cannabis must be undertaken with caution and fully evaluated at each stage to determine the extent to which these changes are leading to increased numbers of users, oversupply, and health risks including cannabis-related harm.
Cdk1-dependent destabilization of long astral microtubules is required for spindle orientation
Authors: Singh Divya , Schmidt Nadine , Müller Franziska , Bange Tanja , Bird Alexander W. 
Published: May 2020

AbstractThe precise execution of mitotic spindle orientation in response to cell shape cues is important for tissue organization and development. The presence of astral microtubules extending from the centrosome towards the cell cortex is essential for this process, but little is understood about the contribution of astral microtubule dynamics to spindle positioning, or how astral microtubule dynamics are regulated spatiotemporally. The mitotic regulator Cdk1-CyclinB promotes destabilization of centrosomal microtubules and increased microtubule dynamics as cells transition from interphase to mitosis, but how Cdk1 activity specifically modulates astral microtubule stability, and whether it impacts spindle positioning, is unknown. Here we uncover a mechanism revealing that Cdk1 destabilizes astral microtubules to ensure spindle reorientation in response to cell shape. Phosphorylation of the EB1-dependent microtubule plus-end tracking protein GTSE1 by Cdk1 in early mitosis abolishes its interaction with EB1 and recruitment to microtubule plus-ends. Loss of Cdk1 activity, or mutation of phosphorylation sites in GTSE1, induces recruitment of GTSE1 to growing microtubule plus-ends in mitosis. This decreases the catastrophe frequency of astral microtubules, and causes an increase in the number of long astral microtubules reaching the cell cortex, which restrains the ability of cells to reorient spindles along the long cellular axis in early mitosis. Astral microtubules must thus not only be present, but also dynamic to allow the spindle to reorient in response to cell shape, a state achieved by selective destabilization of long astral microtubules via Cdk1.
Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets
Authors: Miao Zhen , Balzer Michael S. , Ma Ziyuan , Liu Hongbo , Wu Junnan , Shrestha Rojesh , Aranyi Tamas , Kwan Amy , Kondo Ayano , Pontoglio Marco , Kim Junhyong , Li Mingyao , Kaestner Klaus H. , Susztak Katalin 
Published: May 2020

AbstractDetermining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response.Here, we profiled open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We define key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrated that podocyte commitment occurs early and is associated with sustainedFoxl1expression. Renal tubule cells followed a more complex differentiation, whereHfn4awas associated with proximal andTfap2bwith distal fate. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms.We provide a global single cell resolution view of chromatin accessibility of kidney development. The dataset is available via interactive public websites.
Selective Labeling and Identification of the Tumor Cell Proteome of Pancreatic CancerIn Vivo
Authors: Azizian Nancy G. , Sullivan Delaney K. , Nie Litong , Pardo Sammy , Molleur Dana , Chen Junjie , Weintraub Susan T. , Li Yulin 
Published: May 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers. Dissecting the tumor cell proteome from that of the non-tumor cells in the PDAC tumor bulk is critical for tumorigenesis studies, biomarker discovery, and development of therapeutics. However, investigating the tumor cell proteome has proven evasive due to the tumor’s extremely complex cellular composition. To circumvent this technical barrier, we have combined bioorthogonal non-canonical amino acid tagging (BONCAT) and data-independent acquisition mass spectrometry (DIA-MS) in an orthotopic PDAC model to specifically identify the tumor cell proteomein vivo. Utilizing the tumor cell-specific expression of a mutant tRNA synthetase transgene, this approach provides tumor cells with the exclusive ability to incorporate an azide-bearing methionine analog into newly synthesized proteins. The azide-tagged tumor cell proteome is subsequently enriched and purified via a bioorthogonal reaction and then identified and quantified using DIA-MS. Applying this workflow to the orthotopic PDAC model, we have identified thousands of proteins expressed by the tumor cells. Furthermore, by comparing the tumor cell and tumor bulk proteomes, we showed that the approach can distinctly differentiate proteins produced by tumor-cells from non-tumor cells within the tumor microenvironment. Our study, for the first time, reveals the tumor cell proteome of PDAC under physiological conditions, providing broad applications for tumorigenesis, therapeutics, and biomarker studies in various human cancers.
Improvements in task performance after practice are associated with scale-free dynamics of brain activity
Authors: Kardan Omid , Stier Andrew J. , Layden Elliot A. , Choe Kyoung Whan , Lyu Muxuan , Zhang Xihan , Beilock Sian L. , Rosenberg Monica D. , Berman Marc G. 
Published: May 2020

AbstractAlthough practicing a task generally benefits later performance on that same task, there are individual differences in practice effects. One avenue to model such differences comes from research showing that brain networks extract functional advantages from operating in the vicinity of criticality, a state in which brain network activity is more scale-free. We hypothesized that higher scale-free signal from fMRI data, measured with the Hurst exponent (H), indicates closer proximity to critical states. We tested whether individuals with higherHduring repeated task performance would show greater practice effects. In Study 1, participants performed a dual-n-back task (DNB) twice during MRI (n = 56). In Study 2, we used two runs of n-back task (NBK) data from the Human Connectome Project sample (n = 599). In Study 3, participants performed a word completion task (CAST) across 6 runs (n = 44). In all three studies, multivariate analysis was used to test whether higherHwas related to greater practice-related performance improvement. Supporting our hypothesis, we found patterns of higherHthat reliably correlated with greater performance improvement across participants in all three studies. However, the predictive brain regions were distinct, suggesting that the specific spatialH↑ patterns are not task-general.
Generation of human bronchial organoids for SARS-CoV-2 research
Authors: Suzuki Tatsuya , Itoh Yumi , Sakai Yusuke , Saito Akatsuki , Okuzaki Daisuke , Motooka Daisuke , Minami Shohei , Kobayashi Takeshi , Yamamoto Takuya , Okamoto Toru , Takayama Kazuo 
Published: May 2020

AbstractCoronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. To develop a therapeutic drug for COVID-19, a model that can reproduce the viral life cycle and evaluate the drug efficacy of anti-viral drugs is essential. In this study, we established a method to generate human bronchial organoids (hBO) from commercially available cryopreserved human bronchial epithelial cells and examined whether they could be used as a model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research. Our hBO contain basal, club, ciliated, and goblet cells. Angiotensin-converting enzyme 2 (ACE2), which is a receptor for SARS-CoV-2, and transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike (S) protein of SARS-CoV-2, were highly expressed. After SARS-CoV-2 infection, not only the intracellular viral genome, but also progeny virus, cytotoxicity, pyknotic cells, and moderate increases of the type I interferon signal could be observed. Treatment with camostat, an inhibitor of TMPRSS2, reduced the viral copy number to 2% of the control group. Furthermore, the gene expression profile in SARS-CoV-2-infected hBO was obtained by performing RNA-seq analysis. In conclusion, we succeeded in generating hBO that can be used for SARS-CoV-2 research and COVID-19 drug discovery.Graphical abstract
Reprocessing N95 Respirators During the COVID-19 Pandemic: Moist Heat Inactivates SARS-CoV-2 and Maintains N95 Filtration
Authors: Daeschler Simeon C. , Manson Niclas , Joachim Kariym , Chin Alex W. H. , Chan Katelyn , Chen Paul Z. , Tajdaran Kiana , Mirmoeini Kaveh , Zhang Jennifer J. , Maynes Jason T. , Science Michelle , Darbandi Ali , Stephens Derek , Poon Leo L. M. , Gu Frank , Borschel Gregory H. 
Published: May 2020

AbstractBackgroundThe unprecedented demand and consequent global shortage of N95 respirators during the COVID-19 pandemic have left frontline workers vulnerable to infection. To potentially expand the supply, we validated a rapidly applicable low-cost decontamination protocol in compliance with regulatory standards to enable the safe reuse of personalized, disposable N95-respirators.MethodsFour common models of N95-respirators were disinfected for 60 minutes at 70°C either at 0% or 50% relative humidity (RH). Effective inactivation of SARS-CoV-2 and E. coli was evaluated in inoculated masks. The N95 filter integrity was examined with scanning electron microscopy. The protective function of disinfected N95 respirators was tested against US NIOSH standards for particle filtration efficiency, breathing resistance and respirator fit.ResultsA single heat treatment inactivated both SARS-CoV-2 (undetectable, detection limit: 100 TCID50/ml) and E. coli (0 colonies at 50%RH) in all four respirator models. Even N95-respirators that underwent ten decontamination cycles maintained their integrity and met US-governmental criteria for approval regarding fit, filtration efficiency and breathing resistance. Scanning electron microscopy demonstrated maintained N95 fiber diameter compared to baseline.InterpretationThermal disinfection enables large-scale, low cost decontamination of existing N95 respirators using commonly sourced equipment during the COVID-19 pandemic. This process could be used in hospitals and long term care facilities and also provides a feasible approach to expand the N95 supply in low- and middle-income regions.
Elastin levels are higher in healing tendons than in intact tendons and influence tissue compliance
Authors: Svärd Anna , Hammerman Malin , Eliasson Pernilla 
Published: May 2020

ABSTRACTElastic fibers containing elastin play an important role in tendon functionality, but the knowledge on presence and function of elastin during tendon healing is limited. The aim of this study was to investigate elastin content and distribution in intact and healing Achilles tendons and to understand how elastin influence the viscoelastic properties of tendons. The right Achilles tendon was completely transected in 81 Sprague-Dawley rats. Elastin content was quantified in intact and healing tendons (7, 14, and 28 days post-surgery) and elastin distribution was visualized by immunohistochemistry. Degradation of elastin by elastase incubation was used to study the role of elastin on viscoelastic properties. Mechanical testing was either performed as a cyclic test (20x 10 N) or as a creep test. We found significantly higher levels of elastin in healing tendons at all time-points compared to intact tendons (4% in healing tendons 28 days post-surgery vs 2% in intact tendons). The elastin was more widely distributed throughout the extracellular matrix in the healing tendons in contrast to the intact tendon where the distribution was not so pronounced. Elastase incubation reduced the elastin levels by approximately 30% and led to a 40-50% reduction in creep. This reduction was seen in both intact and healing tendons. Our results show that healing tendons contain more elastin and is more compliable than intact tendons. The role of elastin in tendon healing and tissue compliance indicate a protective role of elastic fibers to prevent re-injuries during early tendon healing.PLAIN LANGUAGE SUMMARYTendons transfer high loads from muscles to bones during locomotion. They are primarily made by the protein collagen, a protein that provide strength to the tissues. Besides collagen, tendons also contain other building blocks such as e.g. elastic fibers. Elastic fibers contain elastin and elastin is important for the extensibility of the tendon. When a tendon is injured and ruptured the tissue heals through scar formation. This scar tissue is different from a normal intact tendon and it is important to understand how the tendons heal. Little is known about the presence and function of elastin during healing of tendon injuries. We have shown, in animal experiments, that healing tendons have higher amounts of elastin compared to intact tendons. The elastin is also spread throughout the tissue. When we reduced the levels of this protein, we discovered altered mechanical properties of the tendon. The healing tendon can normally extend quite a lot, but after elastin removal this extensibility was less obvious. The ability of the healing tissue to extend is probably important to protect the tendon from re-injuries during the first months after rupture. We therefore propose that the tendons heal with a large amount of elastin to prevent re-ruptures during early locomotion.
Autoregulatory circuit regulating basolateral cargo export from the TGN: role of the orphan receptor GPRC5A in PKD signaling and cell polarity
Authors: Di Martino Rosaria , Capalbo Anita , Sticco Lucia , Varavallo Alessandra , Kunnathully Vidya , De Luca Valentina , Iyengar Namrata Ravi , Monte Matteo Lo , Henklein Petra , Cancino Jorge , Luini Alberto 
Published: May 2020

AbstractThe membrane transport apparatus comprises a series of separate membrane bound compartments, or transport stations, that are responsible for the synthesis, processing, transport, sorting and delivery to their final cellular destinations of most transmembrane and soluble lumenal proteins. Over the last decades the membrane transport system has been shown to be extensively regulated both by environmental inputs and by internal homeostatic signalling systems, or control systems, that operate to maintain the homeostasis and optimal functionality of the main transport stations, such as the endoplasmic reticulum and the Golgi, in the face of internal and external perturbations. The trans-Golgi network (TGN) is a major transport and processing station and the main sorting compartment of the transport apparatus. However, the mechanisms that control cargo export and sorting at the TGN have so far remained elusive. Here we focus on the sorting of basolateral cargo proteins and show that these proteins bind to the TGN localized orphan receptor GPRC5A. The cargo-GPRC5A complex triggers the activation of a signaling pathway that involves the Gβγ subunits dependent activation of the phospholipase C beta 3 (PLCβ3), which inturn induces diacyl glycerol (DAG) production. DAG recruits and activates protein kinase D (PKD) and the phosphorylation of its substrates. This step results in the formation of basolateral carriers for delivery of these cargoes to the basolateral plasma membrane domain. We term this mechanism “ARTG” (AutoRegulation ofTGN export). Remarkably, the impairment of ARTG pathway components, and in particular of GPRC5A, causes defects in the polarized organization of epithelial cells.
Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers
Authors: Ruzhanskaya Anna , Ichihara Kiyoshi , Evgina Svetlana , Skibo Irina , Vybornova Nina , Vasiliev Anton , Agarkova Galina , Emanuel Vladimir 
Published: May 2020

AbstractObjectivesA multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 24 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population.MethodsAccording to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 793 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 19 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age.ResultsSDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5%); for insulin, those with BMI≥28 kg/m2(29.9%); for the thyroid panel, those with anti-thyroid antibodies (10.3% in males; 24.5% in females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for α-fetoprotein and all sex-hormones except testosterone. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol, and progesterone, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit.ConclusionRIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.