bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Anatomical Responses of Tolerant and Susceptible European Plum Varieties to Black Knot Disease
Authors: El Kayal Walid , Chamas Zeinab , El-Sharkawy Islam , Subramanian Jayasankar
Published: January 2021

Plums are affected by a cancerous disease called “black knot disease” caused by the fungus Apiosporina morbosa. It affects both Japanese (Prunus salicina) and European (Prunus domestica) plums equally. To understand the spread of the disease, histological analysis was performed in two different European plum cultivars (susceptible and tolerant). Light and scanning electron microscope (SEM) analyses confirmed the presence of the growing hyphae in the internal tissues of the susceptible trees. By using stereoscopic analysis with a fluorescence filter, we were able to detect the hyphae in the visible lesion area. At about 2 inches from above and below the knots, no spore or hypha were visible with the light microscope. However, SEM images showed strong evidence that the fungus is capable of migrating to adjacent vessels in the susceptible plum genotype. In fact, at that distance below and above the knots, conidia were detected inside xylem vessels suggesting a systemic movement of the fungus that has not been shown so far. No symptoms were observed in the resistant genotype. Starch granules, vessel occlusions, and lipid droplets were the main distinguishable characteristics between susceptible and tolerant varieties.
Usitatibacter rugosus gen. nov., sp. nov. and Usitatibacter palustris sp. nov., novel members of Usitatibacteraceae fam. nov. within the order Nitrosomonadales isolated from soil
Authors: Vieira Selma , Huber Katharina J. , Neumann-Schaal Meina , Geppert Alicia , Luckner Manja , Wanner Gerhard , Overmann Jörg
Published: January 2021

Members of the metabolically diverse order

Nitrosomonadales

inhabit a wide range of environments. Two strains affiliated with this order were isolated from soils in Germany and characterized by a polyphasic approach. Cells of strains 0125_3T and Swamp67T are Gram-negative rods, non-motile, non-spore-forming, non-capsulated and divide by binary fission. They tested catalase-negative, but positive for cytochrome c-oxidase. Both strains form small white colonies on agar plates and grow aerobically and chemoorganotrophically on SSE/HD 1 : 10 medium, preferably utilizing organic acids and proteinaceous substrates. Strains 0125_3T and Swamp67T are mesophilic and grow optimally without NaCl addition at slightly alkaline conditions. Major fatty acids are C16 : 1 
ω7c, C16 : 0 and C14 : 0. The major polar lipids are diphosphatidylglycerol, phosphatidylethanolamine and phosphatidyglycerol. The predominant respiratory quinone is Q-8. The G+C content for 0125_3T and Swamp67T was 67 and 66.1 %, respectively. The 16S rRNA gene analysis indicated that the closest relatives (<91 % sequence similarity) of strain 0125_3T were

Nitrosospira multiformis

ATCC 25196T,

Methyloversatilis universalis

FAM5T and

Denitratisoma oestradiolicum

AcBE2-1T, while

Nitrosospira multiformis

ATCC 25196T,

Nitrosospira tenuis

Nv1T and

Nitrosospira lacus

APG3T were closest to strain Swamp67T. The two novel strains shared 97.4 % 16S rRNA gene sequence similarity with one another and show low average nucleotide identity of their genomes (83.8 %). Based on the phenotypic, chemotaxonomic, genomic and phylogenetic analysis, we propose the two novel species Usitatibacter rugosus sp. nov (type strain 0125_3T=DSM 104443T=LMG 29998T=CECT 9241T) and Usitatibacter palustris sp. nov. (type strain Swamp67T=DSM 104440T=LMG 29997T=CECT 9242T) of the novel genus Usitatibacter gen. nov., within the novel family Usitatibacteraceae fam. nov.
ICTV Virus Taxonomy Profile: Nanoviridae
Authors: Thomas John E. , Gronenborn Bruno , Harding Robert M. , Mandal Bikash , Grigoras Ioana , Randles John W. , Sano Yoshitaka , Timchenko Tania , Vetten H. Josef , Yeh Hsin-Hung , Ziebell Heiko ,   ICTV Report Consortium
Published: January 2021

Nanoviridae is a family of plant viruses (nanovirids) whose members have small isometric virions and multipartite, circular, single-stranded (css) DNA genomes. Each of the six (genus Babuvirus) or eight (genus Nanovirus) genomic DNAs is 0.9–1.1 kb and is separately encapsidated. Many isolates are associated with satellite-like cssDNAs (alphasatellites) of 1.0–1.1 kb. Hosts are eudicots, predominantly legumes (genus Nanovirus), and monocotyledons, predominantly in the order Zingiberales (genus Babuvirus). Nanovirids require a virus-encoded helper factor for transmission by aphids in a circulative, non-propagative manner. This is a summary of the ICTV Report on the family Nanoviridae, which is available at ictv.global/report/nanoviridae.
A global phylogenetic analysis of Japanese tonsil-derived Epstein–Barr virus strains using viral whole-genome cloning and long-read sequencing
Authors: Yajima Misako , Kakuta Risako , Saito Yutaro , Kitaya Shiori , Toyoda Atsushi , Ikuta Kazufumi , Yasuda Jun , Ohta Nobuo , Kanda Teru
Published: January 2021

Epstein–Barr virus (EBV) establishes lifelong latent infection in the majority of healthy individuals, while it is a causative agent for various diseases, including some malignancies. Recent high-throughput sequencing results indicate that there are substantial levels of viral genome heterogeneity among different EBV strains. However, the extent of EBV strain variation among asymptomatically infected individuals remains elusive. Here, we present a streamlined experimental strategy to clone and sequence EBV genomes derived from human tonsillar tissues, which are the reservoirs of asymptomatic EBV infection. Complete EBV genome sequences, including those of repetitive regions, were determined for seven tonsil-derived EBV strains. Phylogenetic analyses based on the whole viral genome sequences of worldwide non-tumour-derived EBV strains revealed that Asian EBV strains could be divided into several distinct subgroups. EBV strains derived from nasopharyngeal carcinoma-endemic areas constitute different subgroups from a subgroup of EBV strains from non-endemic areas, including Japan. The results could be consistent with biased regional distribution of EBV-associated diseases depending on the different EBV strains colonizing different regions in Asian countries.
Weighted individual‐resource networks in prey–predator systems: the role of prey availability on the emergence of modular structures
Authors: COSTA Andrea , ROMANO Antonio , ROSA Giacomo , SALVIDIO Sebastiano
Published: January 2021

Ecological networks, usually depicting interactions among species, have been recently down‐scaled to the individual level, permitting description of patterns of inter‐individual resource variation that are usually hindered at the species level. Optimal diet theory (ODT) models, applied to prey–predator systems, predict different patterns of nestedness and modularity in the network, depending on the available resources and intra‐specific competition. The effect of resource availability on the emergence of networks structures, and ODT framework, has not yet fully been clarified. Here, we analyzed the structural patterns of individual‐resource networks in 3 species of Mediterranean salamanders, in relation to changes in prey availability. We used weighted individual‐resource network metrics to interpret the observed patterns, according to 3 ODT models. We found significant nestedness recurring in our study system, indicating that both selective and opportunistic individuals occur in the same population. Prey diversity, rather than abundance, was apparently related to inter‐individual resource variation and promoted the emergence of significant modularity within all networks. The observed patterns of nestedness and modularity, together with the variation in resource diversity and intra‐specific competition, are in agreement with the distinct preferences model of ODT. These findings suggest that in the focal prey–predator systems, individuals were able to perceive changes in prey diversity and to exploit in different ways the variations in composition of available resources, shifting their diet assembly rules accordingly. Our findings also confirm that the use of weighted individual‐resource networks, in prey–predator systems, allows to disclose dynamics that are masked at the species or population level.
Quantifying Structural and Non‐structural Expectations in Relative Clause Processing
Authors: Chen Zhong , Hale John T.
Published: January 2021

Information‐theoretic complexity metrics, such as Surprisal (Hale, 2001; Levy, 2008) and Entropy Reduction (Hale, 2003), are linking hypotheses that bridge theorized expectations about sentences and observed processing difficulty in comprehension. These expectations can be viewed as syntactic derivations constrained by a grammar. However, this expectation‐based view is not limited to syntactic information alone. The present study combines structural and non‐structural information in unified models of word‐by‐word sentence processing difficulty. Using probabilistic minimalist grammars (Stabler, 1997), we extend expectation‐based models to include frequency information about noun phrase animacy. Entropy reductions derived from these grammars faithfully reflect the asymmetry between subject and object relatives (Staub, 2010; Staub, Dillon, & Clifton, 2017), as well as the effect of animacy on the measured difficulty profile (Lowder & Gordon, 2012; Traxler, Morris, & Seely, 2002). Visualizing probability distributions on the remaining alternatives at particular parser states allows us to explore new, linguistically plausible interpretations for the observed processing asymmetries, including the way that expectations about the relativized argument influence the processing of particular types of relative clauses (Wagers & Pendleton, 2016).
Influence of load interaction and hydrogen on fatigue crack growth behavior in steel pipelines under mean load pressure fluctuations
Authors: Tehinse Olayinka , Lamborn Lyndon , Chevil Karina , Gamboa Erwin , Chen Weixing
Published: January 2021

Crack propagation in near neutral pH (NNpH) environment causes significant threat to pipeline integrity. Internal pressure fluctuations during pipeline operation create variable amplitude loading condition that can propagate corrosion fatigue cracks in NNpH environments. This study is aimed at understanding the effect of load interaction due to mean load pressure fluctuations on crack propagation in pipeline steel under NNpH conditions. The loading condition involved underload followed by an overload at set intervals among minor cycles. The effect of minor cycles, magnitude of overload, and NNpH environment were considered and compared to control test in air. Results showed optimum reduction in crack growth rate at low magnitude of overload in mean load pressure fluctuation. Mini striations observed on fracture surface suggest the contributions of minor cycles to crack propagation due to load interaction. Significant increase in crack growth at high magnitude of overload in NNpH environment indicates the influence of hydrogen.
The morphology and evolution of chondrichthyan cranial muscles: A digital dissection of the elephantfish Callorhinchus milii and the catshark Scyliorhinus canicula
Authors: Dearden Richard P. , Mansuit Rohan , Cuckovic Antoine , Herrel Anthony , Didier Dominique , Tafforeau Paul , Pradel Alan
Published: January 2021

The anatomy of sharks, rays, and chimaeras (chondrichthyans) is crucial to understanding the evolution of the cranial system in vertebrates due to their position as the sister group to bony fishes (osteichthyans). Strikingly different arrangements of the head in the two constituent chondrichthyan groups—holocephalans and elasmobranchs—have played a pivotal role in the formation of evolutionary hypotheses targeting major cranial structures such as the jaws and pharynx. However, despite the advent of digital dissections as a means of easily visualizing and sharing the results of anatomical studies in three dimensions, information on the musculoskeletal systems of the chondrichthyan head remains largely limited to traditional accounts, many of which are at least a century old. Here, we use synchrotron tomographic data to carry out a digital dissection of a holocephalan and an elasmobranch widely used as model species: the elephantfish, Callorhinchus milii, and the small‐spotted catshark, Scyliorhinus canicula. We describe and figure the skeletal anatomy of the head, labial, mandibular, hyoid, and branchial cartilages in both taxa as well as the muscles of the head and pharynx. In Callorhinchus, we make several new observations regarding the branchial musculature, revealing several previously unreported or ambiguously characterized muscles, likely homologous to their counterparts in the elasmobranch pharynx. We also identify a previously unreported structure linking the pharyngohyal of Callorhinchus to the neurocranium. Finally, we review what is known about the evolution of chondrichthyan cranial muscles from their fossil record and discuss the implications for muscle homology and evolution, broadly concluding that the holocephalan pharynx is likely derived from a more elasmobranch‐like form which is plesiomorphic for the chondrichthyan crown group. This dataset has great potential as a resource, particularly for researchers using these model species for zoological research, functional morphologists requiring models of musculature and skeletons, as well as for palaeontologists seeking comparative models for extinct taxa.
Glucagon, insulin, adrenocorticotropic hormone, and cortisol in response to carbohydrates and fasting in healthy neonatal foals
Authors: Kinsella Hannah M. , Hostnik Laura D. , Rings Lindsey M. , Swink Jacob M. , Burns Teresa A. , Toribio Ramiro E.
Published: January 2021

Background

The endocrine pancreas and hypothalamic‐pituitary‐adrenal axis (HPAA) are central to energy homeostasis, but information on their dynamics in response to energy challenges in healthy newborn foals is lacking.

Objectives

To evaluate glucagon, insulin, ACTH, and cortisol response to fasting and carbohydrate administration in healthy foals.

Animals

Twenty‐two healthy Standardbred foals ≤4 days of age.

Methods

Foals were assigned to fasted (n = 6), IV glucose (IVGT; n = 5), PO glucose (OGT; n = 5), and PO lactose (OLT; n = 6) test groups. Blood samples were collected frequently for 210 minutes. Nursing was allowed from 180 to 210 minutes. Plasma glucagon, ACTH, serum insulin, and cortisol concentrations were measured using immunoassays.

Results

Plasma glucagon concentration decreased relative to baseline at 45, 90, and 180 minutes during the OLT (P = .03), but no differences occurred in other test groups. Nursing stimulated marked increases in plasma glucagon, serum insulin, and glucose concentrations in all test groups (P < .001). Plasma ACTH concentration increased relative to baseline at 180 minutes (P < .05) during fasting and OLT, but no differences occurred in other test groups. Serum cortisol concentration increased relative to baseline during OLT at 180 minutes (P = .04), but no differences occurred in other test groups. Nursing resulted in decreased plasma ACTH and serum cortisol concentrations in all test groups (P < .01).

Conclusions and Clinical Importance

The endocrine response to enterally and parenterally administered carbohydrates, including the major endocrine response to nursing, suggests that factors in milk other than carbohydrates are strong stimulators (directly or indirectly) of the endocrine pancreas and HPAA.
Line spectrum extraction based on autoassociative neural networks
Authors: Huang Chunlong , Yang Kunde , Yang Qiulong , Zhang Hao
Published: January 2021

Line spectrum is an important feature for the detection and classification of underwater targets. This letter presents a method for extracting the line spectrum submerged in underwater ambient noise through autoassociative neural networks (AANN). Compared with the traditional methods, the proposed method based on AANN can directly enhance the line spectrum from the raw time-domain noise data without relying on prior information and spectral features. Moreover, the proposed method can suppress the background noise while extracting the line spectrum. Both the numerical simulation and experimental data test results demonstrate that the proposed method provides a good ability to extract the line spectrum from the strong background noise.
Disentangling the roles of formant proximity and stimulus prototypicality in adult vowel perception
Authors: Ying Liu Ying , Polka Linda , Masapollo Matthew , Ménard Lucie
Published: January 2021

The present investigation examined the extent to which asymmetries in vowel perception derive from a sensitivity to focalization (formant proximity), stimulus prototypicality, or both. English-speaking adults identified, rated, and discriminated a vowel series that spanned a less-focal/prototypic English /u/ and a more-focal/prototypic French /u/ exemplar. Discrimination pairs included one-step, two-step, and three-step intervals along the series. Asymmetries predicted by both focalization and prototype effects emerged when discrimination step-size was varied. The findings indicate that both generic/universal and language-specific biases shape vowel perception in adults; the latter are challenging to isolate without well-controlled stimuli and appropriately scaled discrimination tasks.
Bilateral and bimodal cochlear implant listeners can segregate competing speech using talker sex cues, but not spatial cues
Authors: Willis Shelby , Xu Kevin , Thomas Mathew , Gopen Quinton , Ishiyama Akira , Galvin John J. , Fu Qian-Jie
Published: January 2021

Cochlear implant (CI) users have greater difficulty perceiving talker sex and spatial cues than do normal-hearing (NH) listeners. The present study measured recognition of target sentences in the presence of two co-located or spatially separated speech maskers in NH, bilateral CI, and bimodal CI listeners; masker sex was the same as or different than the target. NH listeners demonstrated a large masking release with masker sex and/or spatial cues. For CI listeners, significant masking release was observed with masker sex cues, but not with spatial cues, at least for the spatially symmetrically placed maskers and listening task used in this study.
Settings of demersal longlines reveal acoustic cues that can inform toothed whales where and when to depredate
Authors: Richard Gaëtan , Samaran Flore , Guinet Christophe , Bonnel Julien
Published: January 2021

Fishing boats produce acoustic cues while hauling longlines. These acoustic signals are known to be used by odontocetes to detect the fishing activity and to depredate. However, very little is known about potential interactions before hauling. This article describes the acoustic signature of the setting activity. Using passive acoustic recorders attached to the buoys of longlines, this work demonstrates an increase in the ambient sound of ∼6 dB re 1 μPa2 Hz−1 within 2–7 kHz during the setting activity. This could also be used as an acoustic cue by depredating species, suggesting that predators can detect longlines as soon as they are set.
Measurement Reactivity of Accelerometer-Based Sedentary Behavior and Physical Activity in 2 Assessment Periods
Authors: Ullrich Antje , Baumann Sophie , Voigt Lisa , John Ulrich , Ulbricht Sabina
Published: January 2021

Background: The purposes of this study were to examine accelerometer measurement reactivity (AMR) in sedentary behavior (SB), physical activity (PA), and accelerometer wear time in 2 measurement periods and to quantify AMR as a human-related source of bias for the reproducibility of SB and PA estimates. Methods: In total, 136 participants (65% women, mean age = 54.6 y) received 7-day accelerometry at the baseline and after 12 months. Latent growth models were used to identify AMR. Intraclass correlations were calculated to examine the reproducibility using 2-level mixed-effects linear regression analyses. Results: Within each 7-day accelerometry assessment, the participants increased their time spent in SB (b = 2.4 min/d; b = 3.8 min/d) and reduced their time spent in light PA (b = −2.0 min/d; b = −3.2 min/d), but did not change moderate to vigorous PA. The participants reduced their wear time (b = −5.2 min/d) only at the baseline. The intraclass correlations ranged from .42 for accelerometer wear time to .74 for SB. The AMR was not identified as a source of bias in any regression model. Conclusions: AMR may influence SB and PA estimates differentially. Although 7-day accelerometry seems to be a reproducible measure, our findings highlight accelerometer wear time as a crucial confounder in analyzing SB and PA data.
Augmented BMP signaling commits cranial neural crest cells to a chondrogenic fate by suppressing autophagic β-catenin degradation
Authors: Yang Jingwen , Kitami Megumi , Pan Haichun , Nakamura Masako Toda , Zhang Honghao , Liu Fei , Zhu Lingxin , Komatsu Yoshihiro , Mishina Yuji
Published: January 2021

Pathologic BMP signaling promotes ectopic craniofacial cartilage formation by inhibiting the breakdown of β-catenin.
Structural and Biochemical Characterization of the Novel CTX-M-151 Extended-Spectrum β-Lactamase and Its Inhibition by Avibactam
Authors: Ghiglione Barbara , Rodríguez María Margarita , Brunetti Florencia , Papp-Wallace Krisztina M. , Yoshizumi Ayumi , Ishii Yoshikazu , Bonomo Robert A. , Gutkind Gabriel , Klinke Sebastián , Power Pablo
Published: January 2021

The diazabicyclooctane (DBO) inhibitor avibactam (AVI) reversibly inactivates most serine β-lactamases, including the CTX-M β-lactamases. Currently, more than 230 unique CTX-M members distributed in five clusters with less than 5% amino acid sequence divergence within each group have been described.
Amplicon Sequencing-Based Bipartite Network Analysis Confirms a High Degree of Specialization and Modularity for Fungi and Prokaryotes in Deadwood
Authors: Moll Julia , Heintz-Buschart Anna , Bässler Claus , Hofrichter Martin , Kellner Harald , Buscot François , Hoppe Björn
Published: January 2021

Deadwood is important for our forest ecosystems. It feeds and houses many organisms, e.g., fungi and prokaryotes, with many different species contributing to its decomposition and nutrient cycling.
Bartholin gland carcinoma in a young female: a rare disease in an unusual age group
Authors: Akhtar Munazza , Chishti Uzma , Idress Romana
Published: January 2021

Primary Bartholin gland carcinoma (BGC) is an extremely rare disease. It typically presents in elderly women. It can be confused with Bartholin gland cyst, which is a benign condition leading to a delay in diagnosis and treatment. We are presenting a case report of BGC in a 35-year-old woman, which has created a diagnostic as well as therapeutic dilemma.
Multiple firm nodules in a young woman: an unusual presentation of sarcoidosis
Authors: Izadi Firouzabadi Leila , Ghanadan Alireza , Fahim Shabnam , Sadeghinia Ali
Published: January 2021

A 27-year-old woman presented to the dermatology department with a 1-year history of multiple asymptomatic violaceous lesions on her upper and lower extremities, trunk and abdomen. The lesions were firm on palpation. She had no other associated symptoms and the rest of the examination was unremarkable. An incisional biopsy showed multiple confluent granulomas composed of histiocytes devoid of necrosis surrounded by a rim of lymphocytes extending to the subcutaneous fat consistent with the diagnosis of subcutaneous sarcoidosis. The serum ACE assay was elevated at 134 IU/L. Other blood tests including complete blood count, renal and liver function tests, serum calcium and phosphate were within normal ranges and chest X-ray was unremarkable. Complete remission was achieved with an intralesional triamcinolone injection (10 mg/mL) for a few sessions. Subcutaneous sarcoidosis is a rare variation and its diagnosis requires a high index of suspicion.
Changes of the hepatic subcapsular blood flow in a case of high-grade retroperitoneal liposarcoma: what to expect?
Authors: Silva Nádia , Veloso Gomes Filipe , Coelho João Santos , Bilhim Tiago
Published: January 2021

Changes of the hepatic subcapsular blood flow with the early appearance of hypervascularity near the falciform ligament are rare radiologic findings. They present most frequently in cases of superior vena cava (SVC) obstruction and are related to the recruitment of the cavo-mammary-phrenic–hepatic–capsule–portal and the cavo-superficial–umbilical–portal pathways. We present the case of a 52-year-old female patient with an highly aggressive retroperitoneal liposarcoma with SVC obstruction caused by external compression due to a mediastinal metastatic mass. The patient exhibited no symptoms of SVC obstruction due to the collateral cavo-portal pathways.
Psychological complexities of visual restoration
Authors: Dickens Paris , Miller David , Ramaesh Kanna
Published: January 2021

In this paper, we report the psychological and emotional experience of a patient who regained vision after over a decade of vision loss. The negative psychological implications of blindness are well recognised and there is a robust link between visual impairment and low mood and depressive symptoms. Although uncommon, low mood and depressive symptoms have been reported in patients whose sight has been restored, and lack of research gives rise to the possibility their prevalence may be grossly under-recognised in such patient groups. The effects can be so severe that patients may revert to living in darkness in mimicry of their previous lifestyle, effectively obviating the sight-restoring surgery. Healthcare professionals have a responsibility to address this traditionally neglected need by facilitating social, psychological and medical interventions that may ease the return to vision.
Generalised hypomineralisation of enamel in oculodentodigital dysplasia: comprehensive dental management of a case
Authors: Jensen Emilija Daina
Published: January 2021

Oculodentodigital dysplasia (ODDD) is a rare congenital disorder characterised by developmental abnormalities of the eye, dentition and digits of the hands and feet, with neurological symptoms reported in 30% of individuals. Dental anomalies associated with ODDD include enamel hypoplasia and subsequent caries, microdontia, missing teeth, amelogenesis imperfecta, pulp stones and delayed tooth development. Here, we describe the comprehensive dental management of a 3-year-old girl who presented with rapid deterioration of the primary dentition due to generalised enamel hypomineralisation. Conservative, comprehensive restorative management was performed under general anaesthesia. Within 6 months, further breakdown of the remaining unrestored enamel was noted. This case documents the challenges of conservative management in dental anomalies that are not well documented due to the extreme rarity of the disorder.
Acute airway obstruction due to spontaneous intrathyroidal haemorrhage
Authors: Petersen Niels Krintel , Udholm Sebastian , Londero Stefano Christian
Published: January 2021

A woman in her mid-80’s collapsed while home due to a sudden onset of swelling on her neck compromising the airway. She was intubated on-site and brought to the trauma-centre where she was diagnosed with an intrathyroidal bleeding with compression of the trachea. A subacute left sided thyroid lobectomy was performed, giving immediate relief to the displaced and compressed airway. The patient was discharged after 3 days. The final histopathological examination revealed a microfollicular adenoma with extensive bleeding.
Iatrogenic bladder injury from port insertion during laparoscopic appendicectomy
Authors: Lim Chloe Liwen , Neo Shu Hui , Lee Lui Shiong , Sundaram Palaniappan
Published: January 2021

A 26-year-old man underwent laparoscopic appendicectomy for acute appendicitis that was carried out uneventfully after initial urethral catheterisation to empty the bladder. Postoperatively, he developed oliguria associated with high drain output and elevated drain fluid creatinine. A contrast-enhanced computed tomography urography scan showed a small amount of contrast in the intraperitoneal space. A diagnostic laparoscopy performed for a suspected bladder injury revealed that the drain (inserted via the suprapubic port) had traversed the bladder. The drain was removed, and the bladder defects were repaired. The catheter was removed 2 weeks later uneventfully. It is important to recognise and avoid the urinary bladder during suprapubic port insertion during laparoscopic appendicectomy. This complication can be minimised via initial bladder decompression and introduction of the suprapubic port lateral to the umbilical ligaments. A high index of suspicion is required to diagnose a small bladder injury.
Extratemporal intraparotid facial nerve schwannoma
Authors: Chowdhary Stuti , Thangavel Saranya , Ganesan Sivaraman , Alexander Arun
Published: January 2021

Schwannomas of the eighth nerve are common, usually found in syndromic association with neurofibromatosis-2. The occurrence of seventh nerve schwannoma, especially in its extratemporal course, is very rare. Here, we present a case report of an extratemporal facial nerve schwannoma diagnosed preoperatively with cytopathology and postoperative histopathologic confirmation. Histopathology provides the confirmatory diagnosis in such cases. An atypical diagnosis of neural schwannomas should be kept in mind when facial palsy is clinically encountered in the absence of any other aetiological factors.
Feasibility of manual ventilation replacing mechanical ventilation
Authors: Brady Mark F , Weber Nicole K , Walker, III Richard , Holley Joseph E , Ni Samantha A , Young Shane , Monhollon Ethan D , Carpenter Randy S , Tsao Jack W
Published: January 2021

Background

During the COVID-19 pandemic it is anticipated that there will be a shortage of mechanical ventilators available for patients in critical condition. This has sparked many discussions about rationing resources and withholding care; however, an alternative may be to implement manual ventilation in these situations instead. Manual ventilation and a safety device were assessed for efficacy of extended use, such as may be required during this pandemic.

Methods

To evaluate physical output characteristics of extended manual ventilation and efficacy of a barotrauma mitigation device, 47 medical students, nurses and medics completed two 1-hour manual ventilation sessions using the SmartLung 2000 Lung Simulator and 5300 Series Mass Flow Meter with a SPUR II resuscitator bag and endotracheal tube, mimicking a healthy adult with normal lung physiology, both with and without the Sotair device. Providers were randomised to complete their initial session either with or without the Sotair device.

Findings

Collected data show wide variability in tidal volume and peak pressure in unmitigated manual breaths despite prior training and independent exploration of the resuscitation equipment prior to testing. The mean (±SD) tidal volume with bag only was 563.9±128.8 mL and with the safety device 536.1±80.9 mL (p<0.0001). The mean peak inspiratory pressure with bag only was 17.2±6.3 cm H2O and with the safety device 14.9±2.4 cm H2O (p<0.0001).

Interpretation

While extended manual ventilation cannot replace mechanical ventilation, it is feasible with a safety device, which may reduce barotrauma, underventilation and overventilation. These results also demonstrate that withholding care and rationing resources may not be necessary.
Guideline deviation and its association with specific chronic diseases among patients with multimorbidity: a cross-sectional cohort study in a care management setting
Authors: Cohen-Stavi Chandra J , Giveon Shmuel , Key Calanit , Molcho Tchiya , Balicer Ran , Shadmi Efrat
Published: January 2021

Objectives

To assess whether the extent of deviation from chronic disease guideline recommendations is more prominent for specific diseases compared with combined-care across multiple conditions among multimorbid patients, and to examine reasons for this deviation.

Design

A cross-sectional cohort.

Setting

Multimorbidity care management programme across 11 primary care clinics.

Patients

Patients aged 45–95 years with at least two common chronic conditions, sampled according to being new (≤6 months) or veteran (≥1 year) to the programme.

Main outcome measures

Deviation from guideline-recommended care was measured for each patient’s relevant conditions, aggregated and stratified across disease groups, calculated as measures of ‘disease-specific’ guideline deviation and ‘combined-care’ (all conditions) guideline deviation for: atrial fibrillation, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disorder, depression, diabetes, dyslipidaemia, hypertension and ischaemic heart disease. Combined-care deviation was evaluated for its association with specific diseases. Frequencies of previously derived reason types for deviation (biomedical, patient personal and contextual) were reported by nurse care managers, assessed across diseases and evaluated for their association with specific diseases.

Results

Among 204 patients, disease-specific deviation varied more (from 14.7% to 48.2%) across diseases than combined-care deviation (from 14.7% to 25.6%). Depression and diabetes were significantly associated with more deviation (mean: 6% (95% CI: 2% to 10%) and 5% (95% CI: 2% to 9%), respectively). For some conditions, assessments were among small patient samples. Guideline deviation was often attributed to non-disease-specific reasons, such as physical limitations or care burden, as much as disease-specific reasons, which was reflected in the likelihood for guideline deviation to be due to different types of reasons for some diseases.

Conclusions

When multimorbid patients are considered in disease groups rather than as ‘whole persons’, as in many quality of care studies, the cross-cutting factors in their care delivery can be missed. The types of reasons more likely to occur for specific diseases may inform improvement strategies.

Trial registration number

NCT01811173; Pre-results.
Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma
Authors: Aoki Shuichi , Inoue Koetsu , Klein Sebastian , Halvorsen Stefan , Chen Jiang , Matsui Aya , Nikmaneshi Mohammad R , Kitahara Shuji , Hato Tai , Chen Xianfeng , Kawakubo Kazumichi , Nia Hadi T , Chen Ivy , Schanne Daniel H , Mamessier Emilie , Shigeta Kohei , Kikuchi Hiroto , Ramjiawan Rakesh R , Schmidt Tyge CE , Iwasaki Masaaki , Yau Thomas , Hong Theodore S , Quaas Alexander , Plum Patrick S , Dima Simona , Popescu Irinel , Bardeesy Nabeel , Munn Lance L , Borad Mitesh J , Sassi Slim , Jain Rakesh K. , Zhu Andrew X , Duda Dan G
Published: January 2021

Objective

Intrahepatic cholangiocarcinoma (ICC)—a rare liver malignancy with limited therapeutic options—is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role of placental growth factor (PlGF) in ICC progression.

Design

We evaluated the expression of PlGF in specimens from ICC patients and assessed the therapeutic effect of genetic or pharmacologic inhibition of PlGF in orthotopically grafted ICC mouse models. We evaluated the impact of PlGF stimulation or blockade in ICC cells and cancer-associated fibroblasts (CAFs) using in vitro 3-D coculture systems.

Results

PlGF levels were elevated in human ICC stromal cells and circulating blood plasma and were associated with disease progression. Single-cell RNA sequencing showed that the major impact of PlGF blockade in mice was enrichment of quiescent CAFs, characterised by high gene transcription levels related to the Akt pathway, glycolysis and hypoxia signalling. PlGF blockade suppressed Akt phosphorylation and myofibroblast activation in ICC-derived CAFs. PlGF blockade also reduced desmoplasia and tissue stiffness, which resulted in reopening of collapsed tumour vessels and improved blood perfusion, while reducing ICC cell invasion. Moreover, PlGF blockade enhanced the efficacy of standard chemotherapy in mice-bearing ICC.

Conclusion

PlGF blockade leads to a reduction in intratumorous hypoxia and metastatic dissemination, enhanced chemotherapy sensitivity and increased survival in mice-bearing aggressive ICC.
Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19
Authors: Yeoh Yun Kit , Zuo Tao , Lui Grace Chung-Yan , Zhang Fen , Liu Qin , Li Amy YL , Chung Arthur CK , Cheung Chun Pan , Tso Eugene YK , Fung Kitty SC , Chan Veronica , Ling Lowell , Joynt Gavin , Hui David Shu-Cheong , Chow Kai Ming , Ng Susanna So Shan , Li Timothy Chun-Man , Ng Rita WY , Yip Terry CF , Wong Grace Lai-Hung , Chan Francis KL , Wong Chun Kwok , Chan Paul KS , Ng Siew C
Published: January 2021

Objective

Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.

Methods

In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.

Results

Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.

Conclusion

Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
Quantitative morphometrics reveals glomerular changes in patients with infrequent segmentally sclerosed glomeruli
Authors: Schaub Jennifer A , O'Connor Christopher L , Shi Jian , Wiggins Roger C , Shedden Kerby , Hodgin Jeffrey B , Bitzer Markus
Published: January 2021

Aims

Detection of one segmentally sclerosed glomerulus (SSG) identifies patients with focal segmental glomerulosclerosis (FSGS) but rare SSGs may be missed in kidney biopsies. It is unknown whether alterations of unaffected glomeruli in patients with infrequent SSG can be detected by quantitative morphometrics.

Methods

We determined SSG frequency and obtained quantitative morphometrics in glomeruli without a pathologic phenotype in large kidney sections of non-involved kidney tissue from 137 patients undergoing total nephrectomy. We used multivariate modelling to identify morphometrics independently associated with increasing frequency of SSG and Receiver Operator Curve (ROC) analysis to determine the ability of quantitative morphometrics to identify patients with FSGS. We used the geometric distribution to estimate the sensitivity and specificity of a needle biopsy to identify patients with FSGS.

Results

In seventy-one patients (51.8%), at least one SSG was observed, and of those, 39 (54.9%) had an SSG lesion in less than 2% of all glomeruli (mean of 249 glomeruli per specimen). Increasing percent of SSG was independently associated with decreasing podocyte density and increasing mesangial index in multivariate modelling. For infrequent SSG lesions (<1% of glomeruli), kidney biopsy could miss FSGS diagnosis more than 74% of the time, and podocyte density had an area under the curve (AUC) of 0.77, and mesangial index, an AUC of 0.79 to identify patients with FSGS.

Conclusions

More than half of patients had FSGS, although 30% had infrequent SSG. Quantitative morphometrics in glomeruli without pathology, such as podocyte density and mesangial index, identified patients with infrequent SSG and may serve as clinical markers to identify patients with FSGS.
Ally in Fighting Covid-19: Magnitude of Albumin Decline and Lymphopenia (Ally) Predict Progression to Critical Disease
Authors: van Zyl Johanna S , Alam Amit , Felius Joost , Youssef Ronnie M , Bhakta Dipesh , Jack Christina , Jamil Aayla K , Hall Shelley A , Klintmalm Göran B , Spak Cedric W , Gottlieb Robert L
Published: January 2021

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected (Δ) albumin was −0.08 g/dL/day (95% CI −0.11 to −0.04; p<0.001) or four times faster, in those who progressed compared with those who did not progress. A model of Δ albumin combined with lymphocyte percentage predicting progression to critical disease was validated in 60 separate patients (sensitivity, 0.70; specificity, 0.74). ALLY (delta albumin and lymphocyte percentage) is a simple tool to identify patients with COVID-19 at higher risk of disease progression when: (1) a 0.9 g/dL or greater albumin drop from baseline within 5 days of admission or (2) baseline lymphocyte of ≤10% is observed. The ALLY tool identified >70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems.
Association of Vitamin D with Incident Glaucoma: Findings from the Women's Health Initiative
Authors: Carbone Laura D , Johnson Karen , Larson Joseph C , Thomas Fridtjof , Wactawski-Wende Jean , Bollinger Kathryn , Chen Zhao , Watsky Mitchell
Published: January 2021

The relationship between vitamin D and glaucoma is controversial. The objective of this study was to examine women from the Women's Health Initiative (WHI) to determine if there is an association between vitamin D and incident glaucoma in postmenopausal women. We examined the association between dietary vitamin D intake, vitamin D supplements and serum 25 hydroxyvitamin D (25(OH)D) levels and the risk of developing glaucoma. 143,389 postmenopausal women from the WHI including a subset with serum 25(OH) D measurements were examined to determine the association of dietary, supplemental and serum levels of vitamin D to the development of glaucoma. Dietary intakes of vitamin D, use of vitamin D supplements and serum levels of 25(OH) D were predictors examined for the main outcome of incident glaucoma. In multivariable models adjusted for demographic, clinical variables and medication use, dietary vitamin D, vitamin D supplements, total vitamin D intake (diet plus supplements) and serum 25 (OH) D measurements were not significantly associated with incident glaucoma. In the CaD placebo-controlled intervention clinical trial, there was also no association in the active intervention arm with glaucoma. We conclude that dietary vitamin D intake, supplements and serum levels are not significantly related to the risk of developing glaucoma in postmenopausal women.
Ethical climate in contemporary paediatric intensive care
Authors: Moynihan Katie M. , Taylor Lisa , Crowe Liz , Balnaves Mary-Claire , Irving Helen , Ozonoff Al , Truog Robert D. , Jansen Melanie
Published: January 2021

Ethical climate (EC) has been broadly described as how well institutions respond to ethical issues. Developing a tool to study and evaluate EC that aims to achieve sustained improvements requires a contemporary framework with identified relevant drivers. An extensive literature review was performed, reviewing existing EC definitions, tools and areas where EC has been studied; ethical challenges and relevance of EC in contemporary paediatric intensive care (PIC); and relevant ethical theories. We surmised that existing EC definitions and tools designed to measure it fail to capture nuances of the PIC environment, and sought to address existing gaps by developing an EC framework for PIC founded on ethical theory. In this article, we propose a Paediatric Intensive Care Ethical Climate (PICEC) conceptual framework and four measurable domains to be captured by an assessment tool. We define PICEC as the collective felt experience of interdisciplinary team members arising from those factors that enable or constrain their ability to navigate ethical aspects of their work. PICEC both results from and is influenced by how well ethical issues are understood, identified, explored, reflected on, responded to and addressed in the workplace. PICEC encompasses four, core inter-related domains representing drivers of EC including: (1) organisational culture and leadership; (2) interdisciplinary team relationships and dynamics; (3) integrated child and family-centred care; and (4) ethics literacy. Future directions involve developing a PICEC measurement tool, with implications for benchmarking as well as guidance for, and evaluation of, targeted interventions to foster a healthy EC.
Characterisation of the patients with suspected heart failure: experience from the SHEAF registry
Authors: Garg Pankaj , Dakshi Ahmed , Assadi Hosamadin , Swift Andrew J , Naveed Umna , Fent Graham , Lewis Nigel , Rogers Dominic , Charalampopoulos Athanasios , Al-Mohammad Abdallah
Published: January 2021

Objectives

To characterise and risk-stratify patients presenting to a heart failure (HF) clinic according to the National Institute for health and Care Excellence (NICE) algorithm.

Methods

This is an observational study of prospectively collected data in the Sheffield HEArt Failure registry of consecutive patients with suspected HF between April 2012 and January 2020. Outcome was defined as all-cause mortality.

Results

6144 patients were enrolled: 71% had HF and 29% had no HF. Patients with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) >2000 pg/mL were more likely to have HF than those with NT-proBNP of 400–2000 pg/mL (92% vs 64%, respectively). Frequency of HF phenotypes include: HF with preserved ejection fraction (HFpEF) (33%), HF with reduced ejection fraction (HFrEF) (29%), HF due to valvular heart disease (4%), HF due to pulmonary hypertension (5%) and HF due to right ventricular systolic dysfunction (1%). There were 1485 (24%) deaths over a maximum follow-up of 6 years. The death rate was higher in HF versus no HF (11.49 vs 7.29 per 100 patient-years follow-up, p<0.0001). Patients with HF and an NT-proBNP >2000 pg/mL had lower survival than those with NT-proBNP 400–2000 pg/mL (3.8 years vs 5 years, p<0.0001). Propensity matched survival curves were comparable between HFpEF and HFrEF (p=0.88).

Conclusion

Our findings support the use by NICE’s HF diagnostic algorithm of tiered triage of patients with suspected HF based on their NT-proBNP levels. The two pathways yielded distinctive groups of patients with varied diagnoses and prognosis. HFpEF is the most frequent diagnosis, with its challenges of poor prognosis and paucity of therapeutic options.