bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids
Authors: Watanabe Momoko , Haney Jillian R. , Vishlaghi Neda , Turcios Felix , Buth Jessie E. , Gu Wen , Collier Amanda J. , Miranda Osvaldo A. , Chen Di , Sabri Shan , Clark Amander T. , Plath Kathrin , Christofk Heather R. , Gandal Michael J. , Novitch Bennett G. 
Published: December 2019

SUMMARYTelencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of the developing human brain and the underlying causes of many neurological disorders. While progress in organoid technology has been steadily advancing, many challenges remain including rampant batch-to-batch and cell line-to-cell line variability and irreproducibility. Here, we demonstrate that a major contributor to successful cortical organoid production is the manner in which hPSCs are maintained prior to differentiation. Optimal results were achieved using fibroblast-feeder-supported hPSCs compared to feeder-independent cells, related to differences in their transcriptomic states. Feeder-supported hPSCs display elevated activation of diverse TGFβ superfamily signaling pathways and increased expression of genes associated with naïve pluripotency. We further identify combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enable reproducible formation of brain structures suitable for disease modeling.HIGHLIGHTShPSC maintenance conditions influence outcomes in cortical organoid formationIdentification of an intermediate pluripotency state optimal for cortical organoidsFeeder support involves activation of diverse TGFβ signaling pathwaysThe organoid-promoting effects of feeders can be mimicked by a TGFβ factor mixture
Broccoli: combining phylogenetic and network analyses for orthology assignment
Authors: Derelle Romain , Philippe Hervé , Colbourne John K. 
Published: December 2019

AbstractOrthology assignment is a key step of comparative genomic studies, for which many bioinformatic tools have been developed. However, all gene clustering pipelines are based on the analysis of protein distances, which are subject to many artefacts. In this paper we introduce Broccoli, a user-friendly pipeline designed to infer, with high precision, orthologous groups and pairs of proteins using a phylogeny-based approach. Briefly, Broccoli performs ultra-fast phylogenetic analyses on most proteins and builds a network of orthologous relationships. Orthologous groups are then identified from the network using a parameter-free machine learning algorithm. Broccoli is also able to detect chimeric proteins resulting from gene-fusion events and to assign these proteins to the corresponding orthologous groups. Tested on two benchmark datasets, Broccoli outperforms current orthology pipelines. In addition, Broccoli is scalable, with runtimes similar to those of recent distance-based pipelines. Given its high level of performance and efficiency, this new pipeline represents a suitable choice for comparative genomic studies.Broccoli is freely available athttps://github.com/rderelle/Broccoli.
Pull-Push Neuromodulation of Cortical Plasticity Enables Rapid Bi-Directional Shifts in Ocular Dominance
Authors: Hong Su Z. , Huang Shiyong , Severin Daniel , Kirkwood Alfredo 
Published: December 2019

SUMMARYNeuromodulatory systems are essential for remodeling glutamatergic connectivity during experience-dependent cortical plasticity. This permissive/enabling function of neuromodulators has been associated with their capacity to facilitate the induction of Hebbian forms of long-term potentiation (LTP) and depression (LTD) by affecting cellular and network excitability.In vitrostudies indicate that neuromodulators can also affect the expression of Hebbian plasticity in a pull-push manner: receptors coupled to the G-protein Gs promote the expression of LTP at the expense of LTD, and Gq-coupled receptors promote LTD at the expense of LTD. Here we show that the pull-push mechanism can be recruitedin vivoby pairing brief monocular stimulation with pharmacological or chemogenetical activation of Gs- or Gq-coupled receptors to respectively enhance or reduce visual cortical responses. These changes were stable, can be induced in adults after the termination of the critical period for juvenile ocular dominance plasticity, and can rescue deficits induced by prolonged monocular deprivation.
Multiomic and quantitative label-free microscopy-based analysis ofex vivoculture and TGFbeta1 stimulation of human precision-cut lung slices
Authors: Khan Muzamil Majid , Poeckel Daniel , Halavatyi Aliaksandr , Stein Frank , Vappiani Johanna , Sevin Daniel C. , Tischer Christian , Zinn Nico , Eley Jess D , Gudmann Natasja Stæhr , Muley Thomas , Winter Hauke , Fisher Andrew J , Nanthakumar Carmel B. , Bergamini Giovanna , Pepperkok Rainer 
Published: December 2019

AbstractFibrosis can affect any organ resulting in the loss of tissue architecture and function with often life-threatening consequences. Pathologically, fibrosis is characterised by expansion of connective tissue due to excessive deposition of extracellular matrix proteins (ECM), including the fibrillar forms of collagen. A significant hurdle for discovering cures for fibrosis is the lack of suitable models and techniques to quantify mature collagen deposition in tissues. Here we have extensively characterized an ex-vivo cultured human lung derived, precision-cut lung slices model (hPCLS) using live fluorescence light microscopy as well as mass spectrometry-based techniques to obtain a proteomic and metabolomic fingerprint. Using an integrated approach of multiple readouts such as quantitative label-free Second Harmonic Generation (SHG) imaging to measure fibrillar collagen in the extracellular matrix and ELISA-based methods to measure soluble ECM biomarkers, we investigated TGFbeta1-mediated pro-fibrotic signalling in hPCLS. We demonstrate that hPCLS are viable and metabolically active with mesenchymal, epithelial, endothelial, and immune cells surviving for at least two weeks in ex vivo culture. Analysis of hPCLS-conditioned supernatants showed strong induction of ECM synthesis proteins P1NP and fibronectin upon TGFb stimulation. Importantly, this effect translated into an increased deposition of fibrillar collagen in ECM of cultured hPCLS as measured by a novel quantitative SHG-based imaging method only following addition of a metalloproteinase inhibitor (GM6001). Together the data show that an integrated approach of measuring soluble pro-fibrotic markers and quantitative SHG-based analysis of fibrillar collagen is a valuable tool for studying pro-fibrotic signalling and testing anti-fibrotic agents.
Molecular basis of CTCF binding polarity in genome folding
Authors: Nora Elphège P. , Caccianini Laura , Fudenberg Geoffrey , Kameswaran Vasumathi , Nagle Abigail , Uebersohn Alec , So Kevin , Hajj Bassam , Le Saux Agnès , Coulon Antoine , Mirny Leonid A. , Pollard Katherine S. , Dahan Maxime , Bruneau Benoit G. 
Published: December 2019

SummaryCurrent models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin proteins (Merkenschlager & Nora, 2016; Fudenberg, Abdennur, Imakaev, Goloborodko, & Mirny, 2017). While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize DNA loops (de Wit et al., 2015; Guo et al., 2015; Rao et al., 2014; Vietri Rudan et al., 2015), the molecular basis of this polarity remains mysterious. Here we report that CTCF positions cohesin but does not control its overall binding or dynamics on chromatin by single molecule live imaging. Using an inducible complementation system, we found that CTCF mutants lacking the N-terminus cannot insulate TADs properly, despite normal binding. Cohesin remained at CTCF sites in this mutant, albeit with reduced enrichment. Given that the orientation of the CTCF motif presents the CTCF N-terminus towards cohesin as it translocates from the interior of TADs, these observations provide a molecular explanation for how the polarity of CTCF binding sites determines the genomic distribution of chromatin loops.
Therapy without a prescription: buprenorphine/naloxone diversion and the therapeutic assemblage in Taiwan
Authors: Chen Jia‐shin 
Published: December 2019

AbstractBuprenorphine/naloxone (B/N) therapy is a prescription pharmacotherapy for opioid dependence. For certain health service providers, when B/N escapes supervision and diverts into the hands of people for whom it is unintended, it can pose serious risks even if it may still have therapeutic benefits. The line between therapy and diversion is thus a problematic one. By qualitatively analysing archival review and in‐depth interviews, this study uses the concept of a therapeutic assemblage to understand the relationships among government, knowledge, and professionals that surround the regulation of B/N in Taiwan. The therapeutic assemblage is characterised by the partitioning of administration, the loose regulation of prescription, the exclusion of addiction treatment from National Health Insurance (NHI), and the materiality and technicality of therapies. These elements contribute to the therapeutic assemblage's different territorial modes as reflected in the substance schedules that allow for diversion. This is the first grounded work in Asia that empirically examines and theoretically explains the diversion of B/N from an assemblage perspective. It suggests establishing new associations by incorporating addiction treatment into NHI. Lastly, it addresses the analytic purchase of the assemblage approach in unveiling and problematising unintended outcomes of an intervention.
Does prescribing of immediate release oxycodone by emergency medicine physicians result in persistence of Schedule 8 opioids following discharge?
Authors: Veal Felicity , Thompson Angus , Halliday Samuel , Boyles Peter , Orlikowski Chris , Huckerby Emma , Bereznicki Luke 
Published: December 2019

AbstractObjectivesTo identify the prevalence of oxycodone immediate release (IR) prescribed during an ED admission and the persistence of Schedule 8 (S8) opioids following an ED admission.MethodsA retrospective cross‐sectional audit was undertaken reviewing all admission at the ED of the Royal Hobart Hospital, Tasmania, between 1 August and 30 September 2016. The admissions lists for ED were cross matched with the narcotic registers for oxycodone IR (the most commonly supplied S8 in ED) to identify how many patients received IR oxycodone during their ED admissions. Determination of the persistence of opioid use in opioid naïve patients was then undertaken using the Tasmanian real time reporting database of all S8 opioid dispensed in Tasmania (DAPIS).ResultsThere were 8432 ED admissions for 7065 patients aged over 13 years. IR oxycodone was prescribed during 1049 of these admissions (12.4%). Of the patients who were not taking regularly prescribed S8 opioids prior to their ED admission (n = 853), 48 patients (5.6%) were taking S8 opioids at both 2 and 6 months following their ED admission. Thirty patients (2.8%) were approved for authorities for long‐term opioids for non‐cancer pain.ConclusionThese findings suggest that prescribing of IR oxycodone within ED is lower than previous studies. Additionally, the progression to regular chronic opioid use following an ED admission where IR oxycodone was given was relatively low with 3.0% of opioid naïve patients being approved for indications related to chronic non‐cancer pain in the following 6 months.
Improving quality of life for Muslim patients requiring a stoma: A critical review of theological and psychosocial issues
Authors: Habib Abul , Connor Martin J. , Boxall Nicholas E. , Lamb Benjamin W. , Miah Saiful 
Published: December 2019

AbstractAimThe impact of a stoma on the health related quality of life (HRQoL) in patients is irrespective of faith. Muslim patients report lower quality of life and spiritual well‐being following stoma surgery as compared to others. This critical review aims to improve awareness of Islamic practices and HRQoL outcomes in this cohort of patients amongst healthcare professionals.MethodAn extensive non‐systematic search of EMBASE, MEDLINE and Google Scholar was performed for original research articles pertaining to health related quality of life (HRQoL), stoma care and impact on religious practice in Muslim patients. A narrative synthesis of extracted data was performed and presented using basic thematic analysis.ResultsThe findings from the 10 original articles, including 954 participants, were identified. Perceptions of cleanliness emerged as a concern to Muslim patients with stomas as it is core to the performance of prayer. Muslim patients with stomas are known to avoid or reduce participation in prayers due to perceived inferior hygiene and fear of leakage. The consensus opinion from Islamic scholars is that they can pray normally, attend mosque and perform the Hajj pilgrimage. Stoma patients may fast in the holy month of Ramadan provided it is medically safe. Evidence suggests religion‐specific counselling can reduce the detrimental effect on HRQoL of Muslim patients following stoma‐forming surgery and increases engagement in social aspects of life.ConclusionsIt is important for patients, family members and healthcare professionals to understand the practical and religious implications of stomas on these patients for appropriate guidance and counselling.
Fentanyl is used in Mexico's northern border: current challenges for drug health policies
Authors: Fleiz Clara , Arredondo Jaime , Chavez Alfonso , Pacheco Lilia , Segovia Luis A. , Villatoro Jorge A. , Cruz Silvia L. , Medina‐Mora María E. , de la Fuente Juan R. 
Published: December 2019

AbstractBackground and AimsResults from a recent study among 750 heroin users in three Mexico's northern border cities revealed an increase in white powder availability (also known as China white) and preference for this product among heroin users, as well as a general perception of increased overdose cases among this population. Here, we questioned whether those findings reflect an increased presence of heroin laced with fentanyl, which is associated with greater risks of overdose but that, until now, has not been described in Mexico.DesignWe tested fentanyl using highly sensitive test strips in syringe plungers, metal cookers and drug wrappings associated with heroin use.SettingThree injection sites in Tijuana, Baja California, México.ParticipantsEighty‐nine heroin users who interchanged paraphernalia for new syringes.MeasurementsWe tested 59 residues of ‘pure’ white powder. The rest were white powder with black tar (n = 5) or white powder with crystal meth (n = 9), black tar with crystal meth (n = 1), black tar only (n = 13) and crystal meth only (n = 2).FindingsUsers believed that they consumed either white powder heroin, white powder heroin with crystal meth, white powder with black tar heroin or black tar heroin only. Analyses revealed that 93% (n = 55) of the ‘pure’ white powder samples had fentanyl. All (n = 9) the white powder samples mixed with crystal meth and 40% (n = 2) of the white powder with black tar were also laced with fentanyl.ConclusionsIn a sample of 89 heroin users in Mexico, most white powder heroin users were unknowingly exposed to fentanyl, with fentanyl detected in 93% of white powder samples.
Increased DNA methylation in the spermatogenesis‐associated (SPATA) genes correlates with infertility
Authors: Sujit Kumar Mohanty , Singh Vertika , Trivedi Sameer , Singh Kiran , Gupta Gopal , Rajender Singh 
Published: December 2019

AbstractBackgroundSpermatogenesis‐associated (SPATA) family of genes plays important roles in spermatogenesis, sperm maturation or fertilization. The knockout studies in mice have demonstrated that SPATA genes are crucial for fertility. Gene expression and genetic polymorphism studies have further suggested their correlation with infertility; however, methylation analysis of SPATA genes in human male infertility has not yet been undertaken.ObjectivesTo analyze the methylation status of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic male infertility.Materials and methodsIn the present study, we have analyzed DNA methylation pattern in the promoter regions of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic patients and compared it with normozoospermic fertile controls. Semen samples were obtained from 30 oligozoospermic infertile and 19 normozoospermic fertile controls, and DNA methylation levels of the target gene promoters were analyzed by amplicon based deep sequencing methylation analysis using MiSeq.ResultsSPATA4 (P < 0.0008), SPATA5 (P = 0.009) and SPATA6 (Promoter, P < 0.0005; Exon 1, P = 0.0128) genes were significantly hypermethylated in oligozoospermic patients in comparison to controls. This is the first study reporting a higher methylation in the promoters of SPATA4, SPATA5 and SPATA6 in oligozoospermic infertile individuals in comparison to the normozoospermic fertile controls.DiscussionAltered methylation of SPATA genes would affect pathways involved in sperm production or affect various processes linked to sperm fertility.ConclusionIn conclusion, hypermethylation in the SPATA4, SPATA5 and SPATA6 genes correlates with oligozoospermic infertility.
Cleaning potential of different air abrasive powders and their impact on implant surface roughness
Authors: Matsubara Victor H. , Leong Bron W. , Leong Marcus J. L. , Lawrence Zacharij , Becker Thomas , Quaranta Alessandro 
Published: December 2019

AbstractBackgroundImplant surface roughness after air abrasive therapy has not been measured precisely in previous research. Debridement with air abrasion facilitates the mechanical removal of bacterial biofilms but may damage implant surfaces on a microscopic level.PurposeThis study aimed to investigate the cleaning potential of various air abrasive powders and their effect on titanium implant surfaces.Materials and MethodsTwenty implants coated with red ink were inserted into three‐dimensional printed circumferential bone defect models. Treatment was completed with three types of air abrasive powders: sodium bicarbonate (SB), glycine, and erythritol for 60 seconds. Water alone was used as control. The percentage of remaining ink was assessed using digital photography and graphic software. Implant surface topography/roughness was quantified using optical profilometry and examined via scanning electron microscopy. The microscopic analysis was performed at two implant areas: collar (Laser‐Lok surface) and threads.ResultsThe cleaned surfaces (%, mean ± SD) after treatment with SB, glycine, and erythritol accounted for 49.3 ± 3.6%, 33.1 ± 1.2%, and 25.1 ± 0.7%, respectively. Statistically significant differences were found between all groups (P < .001). SB was the only powder that significantly increased the implant roughness (Sa) on both the implant collar (1.53‐2.10 μm) and threads (3.53‐4.20 μm). Regardless of the abrasive powder used, the collar, emerging implant surfaces from the defect base, and surfaces beneath implants threads exhibited more post‐treatment residual ink.ConclusionLarge‐sized powder showed the greatest cleaning capacity, but caused more alterations to the implant surface. Glycine and erythritol displayed no significant changes in surface roughness, however, demonstrated a limited ink removal capacity.
Systematic expression analysis of WEE family kinases reveals the importance of PKMYT1 in breast carcinogenesis
Authors: Liu Yu , Qi Jian , Dou Zhen , Hu Jiliang , Lu Li , Dai Haiming , Wang Hongzhi , Yang Wulin 
Published: December 2019

AbstractObjectivesMany cancer cells depend on G2 checkpoint mechanism regulated by WEE family kinases to maintain genomic integrity. The PKMYT1 gene, as a member of WEE family kinases, participates in G2 checkpoint surveillance and probably links with tumorigenesis, but its role in breast cancer remains largely unclear.Materials and MethodsIn this study, we used a set of bioinformatic tools to jointly analyse the expression of WEE family kinases and investigate the prognostic value of PKMYT1 in breast cancer.ResultsThe results indicated that PKMYT1 is the only frequently overexpressed member of WEE family kinases in breast cancer. KM plotter data suggests that abnormally high expression of PKMYT1 predicts poor prognosis, especially for some subtypes, such as luminal A/B and triple‐negative (TNBC) types. Moreover, the up‐regulation of PKMYT1 was associated with HER2‐positive (HER2+), basal‐like (Basal‐like), TNBC statuses and increased classifications of Scarff, Bloom and Richardson (SBR). Co‐expression analysis showed PKMYT1 has a strong positive correlation with Polo‐like kinase 1 (PLK1), implying they may cooperate in regulating cancer cell proliferation by synchronizing rapid cell cycle with high quality of genome maintenance.ConclusionsCollectively, this study demonstrates that overexpression of PKMYT1 is always found in breast cancer and predicts unfavourable prognosis, implicating it as an appealing therapeutic target for breast carcinoma.
Dermatopathologist assessment of “pathologist‐to‐dermatologist” communication for dermatopathology services
Authors: Sheikh Umar A. , Sufficool Kari E. , Buchanan Paula , Armbrecht Eric S. , Burkemper Nicole M. , Vidal Claudia I. 
Published: December 2019

AbstractBackgroundWhile patients are the ultimate beneficiaries of pathology services, pathologist to clinician communication is an essential component of excellent patient care.ObjectiveTo survey dermatologists on how well pathologists communicate with them and to assess which aspects of pathologists' communication skills are deemed most significant to dermatologists, stratified by practice type.MethodsA survey‐based instrument was developed and sent to dermatologists through various email listservs. Of the approximately 400 potential Association of Professors of Dermatology respondents, 64 returned the survey questionnaire (response rate 16%). Of the 79 state and regional dermatologic societies, seven agreed to distribute the survey on their listservs (response rate 9%).ResultsSurveyed dermatologists believe that the pathologists with whom they work are meeting expectations in the areas of diagnostic accuracy, communicating pertinent information in a timely fashion, integrating written pathology reports into the electronic medical record, and making a clinically meaningful histopathologic interpretation. Discussion of cost of ancillary testing is an area of improvement. University affiliated dermatologists are more likely to use electronic medical records as their predominant mode of communication compared to community dermatologists with and without academic affiliations. Community dermatologists are more likely to use faxed written pathology reports as their predominant mode of communication.ConclusionPhysician‐to‐physician communication is a key component of effective patient care. When it comes to dermatopathology services, dermatologists appear overall satisfied with the indicators examined, however, potential opportunities for improvement exist.