bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid
Authors: Bateson Anna , Ortiz Canseco Julio , McHugh Timothy D. , Witney Adam A. , Feuerriegel Silke , Merker Matthias , Kohl Thomas A. , Utpatel Christian , Niemann Stefan , Andres Sönke , Kranzer Katharina , Maurer Florian P , Ghodousi Arash , Borroni Emanuele , Cirillo Daniela Maria , Wijkander Maria , Toro Juan C. , Groenheit Ramona , Werngren Jim , Machado Diana , Viveiros Miguel , Warren Robin M. , Sirgel Frederick , Dippenaar Anzaan , Köser Claudio U. , Sun Eugene , Timm Juliano 
Published: February 2022

Abstract

Objectives
To develop a robust phenotypic antimicrobial susceptibility testing (AST) method with a correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug.

Methods
The Becton Dickinson Mycobacterial Growth Indicator Tube™ (MGIT) system was used at six laboratories to determine the MICs of a phylogenetically diverse collection of 356 Mycobacterium tuberculosis complex (MTBC) strains to establish the epidemiological cut-off value for pretomanid. MICs were correlated with WGS data to study the genetic basis of differences in the susceptibility to pretomanid.

Results
We observed ancient differences in the susceptibility to pretomanid among various members of MTBC. Most notably, lineage 1 of M. tuberculosis, which is estimated to account for 28% of tuberculosis cases globally, was less susceptible than lineages 2, 3, 4 and 7 of M. tuberculosis, resulting in a 99th percentile of 2 mg/L for lineage 1 compared with 0.5 mg/L for the remaining M. tuberculosis lineages. Moreover, we observed that higher MICs (≥8 mg/L), which probably confer resistance, had recently evolved independently in six different M. tuberculosis strains. Unlike the aforementioned ancient differences in susceptibility, these recent differences were likely caused by mutations in the known pretomanid resistance genes.

Conclusions
In light of these findings, the provisional critical concentration of 1 mg/L for MGIT set by EMA must be re-evaluated. More broadly, these findings underline the importance of considering the global diversity of MTBC during clinical development of drugs and when defining breakpoints for AST.
Early phenotypic detection of fluconazole- and anidulafungin-resistant Candida glabrata isolates
Authors: Georgiou Panagiota-Christina , Arendrup Maiken Cavling , Meletiadis Joseph 
Published: February 2022

Abstract

Background
Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2 protocol was developed for the detection of fluconazole- and anidulafungin-resistant isolates utilizing the colorimetric dye XTT.

Methods
Thirty-one clinical C. glabrata isolates, 11 anidulafungin resistant and 14 fluconazole resistant, were tested. After optimization studies, 0.5–2.5 × 105 cfu/mL of each isolate in RPMI 1640 + 2% d-glucose medium containing 100 mg/L XTT + 0.78 μΜ menadione and 0.06 mg/L anidulafungin (S breakpoint) or 16 mg/L fluconazole (I breakpoint) in 96-well flat-bottom microtitration plates were incubated at 37°C for 18 h; we also included drug-free wells. XTT absorbance was measured at 450 nm every 15 min. Differences between the drug-free and the drug-treated wells were assessed using Student’s t-test at different timepoints. ROC curves were used in order to identify the best timepoint and cut-off.

Results
The XTT absorbance differences between fluconazole-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible increased exposure isolates (0.08 ± 0.05 versus 0.25 ± 0.06, respectively, P = 0.005) at 7.5 h, with a difference of &lt;0.157 corresponding to 100% sensitivity and 94% specificity for detection of resistance. The XTT absorbance differences between anidulafungin-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible isolates (0.08 ± 0.07 versus 0.200 ± 0.03, respectively, P &lt; 0.001) at 5 h, with a difference of &lt;0.145 corresponding to 91% sensitivity and 100% specificity, irrespective of underlying mutations.

Conclusions
A simple, cheap and fast phenotypic test was developed for detection of fluconazole- and anidulafungin-resistant C. glabrata isolates.
Accuracy of preoperative staging of gastric stump cancer
Authors: Kiyokawa Takashi , Fukagawa Takeo , Kaneshiro Shinya , Igarashi Yuuichi , Soeda Naruyoshi , Kumata Yoshimasa , Horikawa Masahiro , Sasajima Yuko , Matsuda Keiji , Fukushima Ryoji 
Published: February 2022

Abstract

Background
In this study, the accuracy of preoperative staging for gastric stump cancer, which has not been thoroughly investigated since the condition is rare, was investigated using computed tomography and gastroscopic imaging.

Methods
Between February 1994 and April 2018, 49 patients with gastric stump cancer, following subtotal or total gastrectomy, were reviewed retrospectively. Preoperative diagnoses of clinical T and clinical N categories were compared with post-operative pathological diagnoses (pT and pN categories). Positive predictive values, accuracy, sensitivity and specificity were also evaluated.

Results
The overall accuracy of T staging was 40.8%. The positive predictive value for cT3/T4 was 96.3%, whereas the positive predictive value for cT1/T2 was 72.7%. The overall accuracy for N staging was 61.2%. The positive predictive value of lymph node positive patients was 73.3%. The positive predictive value and sensitivity of over stage II were 96.6% and 84.8%, respectively.

Conclusions
The accuracy of preoperative diagnosis using both computed tomography and gastroscopy imaging may be feasible for T3/T4 advanced gastric stump cancer, whereas diagnosing T1/2 gastric stump cancer must be carefully considered due to high misdiagnosis rates, relating to depth.
Report of two rare manifestations of abdominal tuberculosis mimicking neoplasia
Authors: Faulhaber Senta , Schindera Sebastian , Hartel Mark , Gräfitsch Alexander 
Published: February 2022

Abstract
Abdominal tuberculosis (TB) can affect any organ of the gastrointestinal tract, and as a result of its unspecific symptoms, it may even mimic neoplasia. Rare manifestations are difficult to detect even for the trained eye and require clinical suspicion. We report rare cases of a mechanical ileus due to peritoneal TB in a 41-year-old man and an isolated peripancreatic infection in a 54-year-old woman. While in one patient, suspected malignancy led to diagnostic laparoscopy, it led to a total pancreatectomy with splenectomy in the other case. However, both times histology ruled out malignancy and showed unexpected similarities with TB. The patients responded well to medical treatment, although one patient is struggling with pancreatogenic diabetes.
PUCHI represses early meristem formation in developing lateral roots of Arabidopsis thaliana
Authors: Bellande Kevin , Trinh Duy-Chi , Gonzalez Anne-Alicia , Dubois Emeric , Petitot Anne-Sophie , Lucas Mikaël , Champion Antony , Gantet Pascal , Laplaze Laurent , Guyomarc’h Soazig 
Published: February 2022

Abstract
Lateral root organogenesis is a key process in the development of a plant’s root system and its adaptation to the environment. During lateral root formation, an early phase of cell proliferation first produces a four-cell-layered primordium, and only from this stage onwards is a root meristem-like structure, expressing root stem cell niche marker genes, being established in the developing organ. Previous studies reported that the gene regulatory network controlling lateral root formation is organized into two subnetworks whose mutual inhibition may contribute to organ patterning. PUCHI encodes an AP2/ERF transcription factor expressed early during lateral root primordium development and required for correct lateral root formation. To dissect the molecular events occurring during this early phase, we generated time-series transcriptomic datasets profiling lateral root development in puchi-1 mutants and wild types. Transcriptomic and reporter analyses revealed that meristem-related genes were expressed ectopically at early stages of lateral root formation in puchi-1 mutants. We conclude that, consistent with the inhibition of genetic modules contributing to lateral root development, PUCHI represses ectopic establishment of meristematic cell identities at early stages of organ development. These findings shed light on gene network properties that orchestrate correct timing and patterning during lateral root formation.
Cell Types in the Thalamus and Cortex
Authors: Martin Usrey W. , Murray Sherman S. 
Published: February 2022

Abstract
The dorsal thalamus and cerebral cortex contain a variety of cell types that form functional circuits. The two major cell types in the thalamus are glutamatergic relay cells with axons that project to the cortex and local GABAergic interneurons. A third group of cells that embryologically are part of the ventral thalamus but play a major role in thalamic circuits of the dorsal thalamus are the GABAergic cells of the thalamic reticular nucleus that integrate feedforward and feedback inputs and provide inhibition to relay cells. The cortex is also comprised of glutamatergic and GABAergic neurons. While some glutamatergic cells are strictly interneurons and others are projection neurons that also provide local input, GABAergic neurons are all interneurons. These cell types form circuits within the cortex that have stereotypical patterns of connectivity between the six cortical layers as well as with other cortical and subcortical structures, including, importantly, the thalamus. This chapter explores the cell types and connections of neurons in the thalamus and cortex.
Thalamic Circuitry
Authors: Martin Usrey W. , Murray Sherman S. 
Published: February 2022

Abstract
This chapter delves into details of thalamic circuitry, using the lateral geniculate nucleus as an initial model. Three major sources of input to relay cells exist: drivers (e.g., retinal input), a feedback from layer 6 of cortex, local GABAergic input from interneurons and cells of the thalamic reticular nucleus, and classic modulatory inputs from various brainstem sources. Surprisingly, driver input produces only about 5% of all synapses onto relay cells. The remaining inputs (layer 6 of cortex, local GABAergic, and brainstem modulatory) each contribute 30–40% of the synaptic input. The patterns of non-driver inputs are relatively consistent among thalamic nuclei and mammalian species. An unusual aspect of thalamic circuitry is the triadic synaptic arrangement, in which a terminal from the driving input synapses onto both a relay cell dendrite and onto a GABAergic dendritic terminal from an interneuron and the same interneuronal terminal synapses onto the same relay cell dendrite; the interneuronal process is thus both pre- and postsynaptic. Possible functions of the triadic circuitry are discussed. Also discussed are some quantitative differences in synaptic organization between first and higher order relays.
Thalamocortical Substrates of Attention
Authors: Martin Usrey W. , Murray Sherman S. 
Published: February 2022

Abstract
Selective attention is a cognitive process that allows an organism to direct processing resources to behaviorally relevant stimuli. Attention has clear benefits for survival, as attention improves reaction time as well as the discrimination of stimuli. Although most studies of attention have been focused on effects within the cortex, increasing evidence demonstrates attention affects thalamic processing and thalamocortical network activity. This chapter examines the influence of visual attention on the response properties of different classes of thalamic neurons and their network interactions within the thalamus and with the cortex. The neural mechanisms of attention also include evolutionarily older structures, and ideas are explored regarding the integration of older and more recent brain circuits for attention.
Corticothalamic Circuits Linking Sensation and Action
Authors: Martin Usrey W. , Murray Sherman S. 
Published: February 2022

Abstract
Anatomical data show that most or all driving inputs to thalamus arrive via branching axons, with many targets of the extrathalamic branches being motor centers in the brainstem and/or spinal cord. The interpretation of this is that the messages sent to thalamus for relay are exact copies of messages intended to create and/or influence a motor action. Such a copy can be regarded as an efference copy. This leads to the speculation that one of the differences in the messages sent via direct and transthalamic corticocortical pathways is that the latter can serve as efference copies to inform the target cortical areas of a motor message sent out by the afferent area. It is also suggested from an evolutionary perspective that efference copies exist at multiple levels—spinal, brainstem, and cortical—and that this idea implies that the central nervous system is challenged to deal effectively with all of these efference copies; how it does so remains to be determined.
Conclusions
Authors: Martin Usrey W. , Murray Sherman S. 
Published: February 2022

Abstract
This final chapter reflects on the topics, viewpoints, and speculation provided throughout the book. At the outset, the authors’ goal was to provide information essential for understanding and thinking about thalamocortical interactions and then to go one step further, to provide fresh perspective and new ideas that sometimes challenge current thinking. This chapter includes a list of several “take-away points to ponder” and a final discussion on “why do we have a thalamus?” The hope is that this book will stimulate further thinking and, hopefully, plant a few seeds for the generation of new and testable ideas that will further advance our understanding of thalamocortical interactions and their critical role in brain function.
Oesophageal tumours
Authors: Foley Kieran , Morgan Carys , Crosby Tom 
Published: February 2022

Abstract
Chapter 7 discusses oesophageal tumours, including clinical background, diagnosis and staging, planning, therapeutic assessment, and follow-up. Patients with oesophageal cancer have a poor prognosis because many present with advanced disease. Accurate multi-modality staging with computed tomography (CT), endoscopic ultrasound (EUS), and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) is vital for management decisions, in particular providing complementary information for radical radiotherapy planning. The role of radiological imaging to assess treatment response is an area of growing interest. The likelihood of disease recurrence following potentially curative therapy remains high but the benefit of post-treatment surveillance remains unproven.
Gastric tumours
Authors: Carroll Nicholas , Smyth Elizabeth C. 
Published: February 2022

Abstract
Chapter 8 discusses gastric tumours. Gastric adenocarcinoma is the fifth most common cancer globally and the third most common cause of cancer death. Although diagnosis is largely by endoscopy, imaging is integral to accurate staging and subsequent treatment decisions. The mobility and volume changes of the stomach can make interpretation of imaging difficult unless measures are taken to compensate for the differences in volume and relative collapse or distension of the mucosa and gastric wall. Other tumour types include lymphoma, stromal tumours, and metastases, but this chapter will focus on the imaging of adenocarcinoma. In addition there is a crossover between pure gastric tumours and tumours of the gastroesophageal junction. These are subclassified into Siewert types I, II, and III, the latter centred in the proximal stomach. The type III tumours are therefore staged and managed as gastric cancers.
Gastrointestinal stromal tumours
Authors: Choi Haesun 
Published: February 2022

Abstract
Gastrointestinal stromal tumour (GIST) is rare, but the most common tumour of non-epithelial origin in the GI tract. It was often misdiagnosed as leiomyomas and leiomyosarcomas, with a dismal prognosis until KIT receptor protein was identified in the tumour cells. GISTs are now thought to derive from a precursor of the interstitial cells of Cajal, which are normally present in the myenteric plexus, and are clearly distinct from other mesenchymal tumours. GISTs typically present with non-specific gastrointestinal symptoms and surgical resection is the only cure, but it most frequently presents with a large, non-resectable or marginally resectable mass. It is one of the solid tumours that took advantage of the early targeted agents, KIT tyrosine kinase receptor inhibitor, such as imatinib, with dramatic improvement of the survival. Prolonged survival with GISTs has been increasingly recognized and the role of imaging has become important not only for diagnosing and staging the tumours, but also for monitoring the tumours during and following treatments. This chapter will review the clinical presentation, diagnosis, current management, and role of imaging in management of GISTs.
Urological cancers
Authors: Choudhury Ananya , Hoskin Peter 
Published: February 2022

Abstract
Prostate cancer is the most common cancer in males. There have been significant advances in imaging over the past decade, leading to improvements in diagnosis, staging, response assessment, and patient follow-up. This chapter covers urological cancers, including prostate cancer, bladder cancer, upper urinary tract urothelial tumours, testicular cancer, penile cancer, renal cell carcinoma, and urethral cancer. The current gold standard in imaging is discussed, with a look at imaging modalities on the horizon which are likely to impact cancer treatment in the next few years. Ultrasound, cross-sectional and radioisotope imaging all have a place in the management of urological cancers and radiotherapy planning.
Imaging for common complications
Authors: Addley Helen , Hickman Katy , Ajithkumar Thankamma 
Published: February 2022

Abstract
Chapter 22 covers the imaging manifestations of common complications that arise from both the cancer disease process and the therapies used to treat cancer. We discuss how imaging plays a critical role in the detection, evaluation, and management of complications. Emergency conditions that develop in oncology patients secondary to the disease require timely imaging studies. These include conditions such as pulmonary embolism, superior vena cava obstruction, metastatic epidural spinal cord compression, abdominal emergencies including bowel obstruction, perforation, and bowel ischaemia, as well as the range of manifestations of sepsis. Complications also arise as a direct result of treatment, whether that be chemotherapy, radiotherapy, or immunotherapy. We will cover treatment related complications such as lung injury secondary to radiotherapy and chemotherapy, insufficiency fractures, and the range of complications associated with immunotherapy, including hepatitis, hypophysitis, colitis, and pneumonitis.
Teaching
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie 
Published: February 2022

Abstract
This chapter contains 15 different teaching sample cases for the Fellowship of the Royal College of Emergency Medicine (FRCEM) Objective Structured Clinical Examination (OSCE). In this chapter, candidates are provided with the opportunity to teach a variety of concepts such as examinations, practical procedures and skills, and theory of key concepts. There is a strong focus on teaching technique, communication skills, knowledge, and application of up-to-date guidelines. The cases reflect a range of common presentations that are pertinent to the Royal College of Emergency Medicine (RCEM) curriculum and that are seen in real-life Emergency Departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and a mark scheme. Key learning points are highlighted after each case.
Psychiatry Scenarios
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie 
Published: February 2022

Abstract
Chapter 8 contains 6 different psychiatry sample cases for the FRCEM OSCE. In this chapter, candidates must be able to take a psychiatric history, assess mental state and capacity in the context of deliberate self-harm and mental disorder. This chapter also covers taking an alcohol history, assessing cognition using a MMSE. The cases reflect a range of common presentations that are pertinent to the RCEM curriculum and that are seen in real life Emergency Departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and mark scheme. Key learning points are highlighted after each case.
Management Scenarios
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie 
Published: February 2022

Abstract
This chapter contains eight management sample cases for the Fellowship of the Royal College of Emergency Medicine (FRCEM) Objective Structured Clinical Examination (OSCE). This chapter provides candidates with a framework to approach senior management scenarios common in the emergency department. These include personnel- and patient-related situations. This will incorporate previously learnt communication skills. Candidates must incorporate communication skills, knowledge, and management skills to successfully negotiate the scenarios. The cases reflect a range of common presentations that are pertinent to the Royal College of Emergency Medicine (RCEM) curriculum and that are seen in real-life emergency departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and a mark scheme. Key learning points are highlighted.
The origin of star–gas misalignments in simulated galaxies
Authors: Casanueva Catalina I , Lagos Claudia del P , Padilla Nelson D , Davison Thomas A 
Published: February 2022

ABSTRACT
We study the origin of misalignments between the stellar and star-forming gas components of simulated galaxies in the eagle simulations. We focus on galaxies with stellar masses ≥109 M⊙ at 0 ≤ z ≤ 1. We compare the frequency of misalignments with observational results from the SAMI survey and find that overall, eagle can reproduce the incidence of misalignments in the field and clusters, as well as the dependence on stellar mass and optical colour within the uncertainties. We study the dependence on kinematic misalignments with internal galaxy properties and different processes related to galaxy mergers and sudden changes in stellar and star-forming gas mass. We find that galaxy mergers happen in similar frequency in mis- and aligned galaxies, with the main difference being misaligned galaxies showing a higher tidal field strength and fraction of ex situ stars. We find that despite the environment being relevant in setting the conditions to misalign the star-forming gas, the properties internal to galaxies play a crucial role in determining whether the gas quickly aligns with the stellar component or not. Hence, galaxies that are more triaxial and more dispersion dominated display more misalignments because they are inefficient at realigning the star-forming gas towards the stellar angular momentum vector.