We present barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel insitu analyses (BOLORAMIS), a reverse transcription-free method for spatially-resolved, targeted, in situ RNA identification of single or multiple targets. BOLORAMIS was demonstrated on a range of cell types and human cerebral organoids. Singleplex experiments to detect coding and non-coding RNAs in human iPSCs showed a stem-cell signature pattern. Specificity of BOLORAMIS was found to be 92% as illustrated by a clear distinction between human and mouse housekeeping genes in a co-culture system, as well as by recapitulation of subcellular localization of lncRNA MALAT1. Sensitivity of BOLORAMIS was quantified by comparing with single molecule FISH experiments and found to be 11%, 12% and 35% for GAPDH, TFRC and POLR2A, respectively. To demonstrate BOLORAMIS for multiplexed gene analysis, we targeted 96 mRNAs within a co-culture of iNGN neurons and HMC3 human microglial cells. We used fluorescence in situ sequencing to detect error-robust 8-base barcodes associated with each of these genes. We then used this data to uncover the spatial relationship among cells and transcripts by performing single-cell clustering and gene-gene proximity analyses. We anticipate the BOLORAMIS technology for in situ RNA detection to find applications in basic and translational research.
OBJECTIVE: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children.
SUMMARY OF BACKGROUND DATA: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS.
METHODS: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS.
RESULTS: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications.
CONCLUSION: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
Psychological science tends to treat subjective well-being and happiness synonymously. We start from the assumption that subjective well-being is more than being happy to ask the fundamental question: What is the ideal level of happiness? From a cross-cultural perspective, we propose that the idealization of attaining maximum levels of happiness may be especially characteristic of Western, educated, industrial, rich, and democratic (WEIRD) societies but less so for others. Searching for an explanation for why "happiness maximization" might have emerged in these societies, we turn to studies linking cultures to their eco-environmental habitat. We discuss the premise that WEIRD cultures emerged in an exceptionally benign ecological habitat (i.e., faced relatively light existential pressures compared with other regions). We review the influence of the Gulf Stream on the Northwestern European climate as a source of these comparatively benign geographical conditions. We propose that the ecological conditions in which WEIRD societies emerged afforded them a basis to endorse happiness as a value and to idealize attaining its maximum level. To provide a nomological network for happiness maximization, we also studied some of its potential side effects, namely alcohol and drug consumption and abuse and the prevalence of mania. To evaluate our hypothesis, we reanalyze data from two large-scale studies on ideal levels of personal life satisfaction-the most common operationalization of happiness in psychology-involving respondents from 61 countries. We conclude that societies whose members seek to maximize happiness tend to be characterized as WEIRD, and generalizing this across societies can prove problematic if adopted at the ideological and policy level.
TABLE OF CONTENTS: A1 Point-of-care ultrasound examination of cervical spine in emergency departmentYahya Acar, Onur Tezel, Necati SalmanA2 A new technique in verifying the placement of a nasogastric tube: obtaining the longitudinal view of nasogastric tube in addition to transverse view with ultrasoundYahya Acar, Necati Salman, Onur Tezel, Erdem CevikA3 Pseudoaneurysm of the femoral artery after cannulation of a central venous line. Should we always use ultrasound in these procedures?Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-BordomásA4 Ultrasound-guided supraclavicular subclavian vein catheterization. A novel approach in emergency departmentMargarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-BordomásA5 Clinical ultrasound in a septic and jaundice patient in the emergency departmentMargarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-BordomásA6 Characterization of the eyes in preoperative cataract Saudi patients by using medical diagnostic ultrasoundMustafa Z. Mahmoud, Abdelmoneim SuliemanA7 High-frequency ultrasound in determining the causes of acute shoulder joint painMustafa Z. MahmoudA8 Teaching WINFOCUS Ultrasound Life Support Basic Level 1 for Providers in resource-limited countriesAbbas Ali, Alrayah Mustafa, Ihab Abdelrahman, Mustafa Bahar, Osama Ali, H. Lester Kirchner, Gregor ProsenA9 Changes of arterial stiffness and endothelial function during uncomplicated pregnancyAjda Anzic, Paul LeesonA10 Cardiovascular haemodynamic properties before, during and after pregnancyAjda Anzic, Paul LeesonA11 An old man with generalized weaknessMaryam Bahreini, Fatemeh RasooliA12 Ultrasonography for non-specific presentations of abdominal painMaryam Bahreini, Houman HosseinnejadA13 Introduction of a new imaging guideline for suspected renal colic in the emergency department: effect on CT Urogram utilisationGabriel Blecher, Robert Meek, Diana Egerton-WarburtonA14 Transabdominal ultrasound screening for pancreatic cancer in Croatian military veterans: a retrospective analysis from the first Croatian veteran's hospitalEdina Ćatić Ćuti, Stanko Belina, Tihomir Vančina, Idriz KovačevićA15 The challenge of AAA: unusual case of obstructive jaundiceEdina Ćatić Ćuti, Nadan RustemovićA16 Educational effectiveness of easy-made new simulator model for ultrasound-guided procedures in pediatric patients: vascular access and foreign body managementIkwan Chang, Jin Hee Lee, Young Ho Kwak, Do Kyun KimA17 Detection of uterine rupture by point-of-care ultrasound at emergency department: a case reportChi-Yung Cheng, Hsiu-Yung Pan, Chia-Te KungA18 Abdominal probe in the hands of interns as a relevant diagnostic tool in revealing the cause of heart failureEla Ćurčić, Ena Pritišanac, Ivo Planinc, Marijana Grgić Medić, Radovan RadonićA19 Needs assessment of the potential utility of point-of-care ultrasound within the Zanzibar health systemAbiola Fasina, Anthony J. Dean, Nova L. Panebianco, Patricia S. HenwoodA20 Ultrasonographic diagnosis of tracheal compressionOliviero Fochi, Moreno Favarato, Ezio BonanomiA21 The role of ultrasound in the detection of lung infiltrates in critically ill patients: a pilot studyMarijana Grgić Medić, Ivan Tomić, Radovan RadonićA22 The SAFER Lasso; a novel approach using point-of-care ultrasound to evaluate patients with abdominal complaints in the emergency departmentYoungrock Ha, Hongchuen TohA23 Awareness and use of clinician-performed ultrasound among clinical clerkship facultyElizabeth Harmon, Wilma Chan, Cameron Baston, Gail Morrison, Frances Shofer, Nova Panebianco, Anthony J. DeanA24 Clinical outcomes in the use of lung ultrasound for the diagnosis of pediatric pneumoniasAngela Hua, Sharon Kim, James TsungA25 Effectiveness of ultrasound in hypotensive patientsIsa Gunaydin, Zeynep Kekec, Mehmet Oguzhan AyA26 Moderate-to-severe left ventricular ejection fraction related to short-term mortality of patients with post-cardiac arrest syndrome after out-of-hospital cardiac arrestJinjoo Kim, Jinhyun Kim, Gyoosung Choi, Dowon ShimA27 Usefulness of abdominal ultrasound for acute pyelonephritis diagnosis after kidney transplantationJi-Han LeeA28 Lung ultrasound for assessing fluid tolerance in severe preeclampsiaJana Ambrozic, Katja Prokselj, Miha LucovnikA29 Optic nerve sheath ultrasound in severe preeclampsiaGabrijela Brzan Simenc, Jana Ambrozic, Miha LucovnikA30 Focused echocardiography monitoring in the postoperative period for non-cardiac patientsAsta Mačiulienė, Almantas Maleckas, Algimantas Kriščiukaitis, Vytautas Mačiulis, Andrius MacasA31 POCUS-guided paediatric upper limb fracture reduction: algorithm, tricks, and tipsSharad MohiteA32 Point-of-care lung ultrasound: a good diagnostic tool for pneumonia in a septic patientZoltan Narancsik, Hugon MožinaA33 A case of undergraduate POCUS (r)evolutionSara Nikolić, Jan Hansel, Rok Petrovčič, Una Mršić, Gregor ProsenA34 The Graz Summer School for ultrasound: from first contact to bedside application: three-and-a-half-day undergraduate ultrasound training: résumé after two years of continuous developmentSimon Orlob, Markus Lerchbaumer, Niklas Schönegger, Reinhard KaufmannA35 Usefulness of point-of-care ultrasound in the emergency room in a patient with acute abdominal painAlberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-BordomásA36 Use of bedside ultrasound in a critically ill patient. A case reportAlberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-BordomásA37 Diagnostic yield of clinical echocardiography for the emergency physicianAlberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-BordomásA38 Focused cardiac ultrasound in early diagnosis of type A aortic dissection with atypical presentationChun-I Pan, Hsiu-Yung Pan, Chien-Hung WuA39 Detection of imperforated hymen by point-of-care ultrasoundHsiu-yung Pan, Chia-Te KungA40 Developing a point-of-care ultrasound curriculum for pediatric nurse practitioners practicing in the pediatric emergency departmentSarah Pasquale, Stephanie J. Doniger, Sharon Yellin, Gerardo ChiricoloA41 Use of transthoracic echocardiography in emergency setting: patient with mitral valve abscessMaja Potisek, Borut Drnovšek, Boštjan LeskovarA42 A young man with syncopeFatemeh Rasooli, Maryam BahreiniA43 Work-related repetitive use injuries in ultrasound fellowsKristine Robinson, Clara Kraft, Benjamin Moser, Stephen Davis, Shelley Layman, Yusef Sayeed, Joseph MinardiA44 Lung ultrasonography in the evaluation of pneumonia in childrenIrmina Sefic Pasic, Amra Dzananovic, Anes Pasic, Sandra Vegar ZubovicA45 Central venous catheter placement with the ultrasound aid: two years' experience of the Interventional unit, Division of Intensive Care Medicine, KBC ZagrebAna Godan Hauptman, Marijana Grgic Medic, Ivan Tomic, Ana Vujaklija Brajkovic, Jaksa Babel, Marina Peklic, Radovan RadonicA46 Duplicitas casui: two patients admitted due to acute liver failureVedran Radonic, Ivan Tomic, Luka Bielen, Marijana Grgic MedicA47 A pilot survey on an understanding of Bedside Point-of-Care Ultrasound (POCUS) among medical doctors in internal medicine: exposure, perceptions, interest, and barriers to trainingPeh Wee MingA48 Unusual case of defecation syncopeNur hafiza Yezid, Fatahul Laham MohammedA49 A case report of massive pulmonary embolism; a multidisciplinary approachZainal Abidin Huda, Wan Nasarudin Wan Ismail, W.Yus Haniff W.Isa, Hashairi Fauzi, Praveena Seeva, Mohd Zulfakar Mazlan.
A search for the rare η→μ^{+}μ^{-}μ^{+}μ^{-} double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101 fb^{-1}. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ^{+}μ^{-} decay as normalization, the branching fraction B(η→μ^{+}μ^{-}μ^{+}μ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2μ})]×10^{-9} is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions.
A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section σ(pp→A^{'}→χ_{1}χ_{2}) and the decay branching fraction B(χ_{2}→χ_{1}μ^{+}μ^{-}), where A^{'} is a dark photon and χ_{1} and χ_{2} are states in the dark sector with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.
The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138 fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.
A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13 TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135 fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst) MeV. Another structure with even higher significance is found at a mass of 6847_{-28}^{+44}(stat)_{-20}^{+48}(syst) MeV, which is consistent with the X(6900) resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134_{-25}^{+48}(stat)_{-15}^{+41}(syst) MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference.
The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138 fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling) fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.
The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.