bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the halo sign in the assessment of giant cell arteritis: a systematic review and meta-analysis
Authors: Sebastian Alwin , Coath Fiona , Innes Sue , Jackson Jo , van der Geest Kornelis S M , Dasgupta Bhaskar
Published: August 2021

Objectives

This systematic review and meta-analysis aimed to evaluate the diagnostic value of the halo sign in the assessment of GCA.

Methods

A systematic literature review was performed using MEDLINE, EMBASE and Cochrane central register databases up to August 2020. Studies informing on the sensitivity and specificity of the US halo sign for GCA (index test) were selected. Studies with a minimum of five participants were included. Study articles using clinical criteria, imaging such as PET-CT and/or temporal artery biopsy (TAB) as the reference standards were selected. Meta-analysis was conducted with a bivariate model.

Results

The initial search yielded 4023 studies. Twenty-three studies (patients n = 2711) met the inclusion criteria. Prospective (11 studies) and retrospective (12 studies) studies in academic and non-academic centres were included. Using clinical diagnosis as the standard (18 studies) yielded a pooled sensitivity of 67% (95% CI: 51, 80) and a specificity of 95% (95% CI: 89, 98%). This gave a positive and negative likelihood ratio for the diagnosis of GCA of 14.2 (95% CI: 5.7, 35.5) and 0.375 (95% CI: 0.22, 0.54), respectively. Using TAB as the standard (15 studies) yielded a pooled sensitivity of 63% (95% CI: 50, 75) and a specificity of 90% (95% CI: 81, 95).

Conclusion

The US halo sign is a sensitive and specific approach for GCA assessment and plays a pivotal role in diagnosis of GCA in routine clinical practice.

Registration

PROSPERO 2020 CRD42020202179.
The Cerebellum Links to Positive Symptoms of Psychosis: A Systematic Review and Meta-analysis
Authors: Pinheiro Ana P , Johnson Joseph F , Amorim Maria , Roberto Magda , Schwartze Michael , Kotz Sonja A , Shenton Martha E
Published: August 2021

Background

Positive symptoms of psychosis may be the result of faulty coordination and automatization of motor and higher order cognitive functions, partly due to cerebellar dysfunction. Specifically, auditory verbal hallucinations (AVH) have been related to altered processing of sensory feedback to one’s own action. Such alterations highlight the role of dysfunctional cerebellar circuitry in psychosis. However, how exactly the cerebellum contributes to AVH remains unclear.

Methods

A systematic search of electronic databases identified a broad range of cerebellar neuroimaging studies in psychotic patients, reporting volume, structural connectivity, or resting-state functional connectivity data. A total of 22 studies were selected for review: 11 focused on the specific effects of AVH and 11 probed the effects of aggregated positive symptom scores. Meta-analysis was used to probe the consistency of cerebellar differences and their relationship with sociodemographic and clinical measures. An exploratory activation likelihood estimation (ALE) analysis tested the regional specificity of cerebellar differences in patients with such symptoms.

Results

Cerebellar differences were more consistently associated with AVH than with aggregated positive symptom measures, particularly when considering resting-state functional connectivity data. These differences were not moderated by age, sex, medication, or symptom severity. The ALE meta-analysis revealed a spatial convergence of these differences in lobules V–VI and crus I.

Conclusions

Cerebellar dysconnectivity might indicate a specific liability for AVH, particularly in sensorimotor (lobules V–VI) and cognitive (crus I) cerebellar zones. These abnormalities may contribute to altered sensory feedback processing and, consequently, affect higher level cognitive functions (eg, cognitive control) in AVH.
Prevalent Transmission of ‘Candidatus Liberibacter asiaticus’ over ‘Ca. Liberibacter americanus’ in a Long-Term Controlled Environment
Authors: Gasparoto Maria Cândida de Godoy , Primiano Isabela Vescove , Bassanezi Renato B. , Lourenço Silvia Afonseca , Montesino Luiz H. , Wulff Nelson Arno , Martins Elaine Cristina , Filho Armando Bergamin , Amorim Lilian
Published: August 2021

In Brazil, citrus huanglongbing (HLB) is associated with ‘Candidatus Liberibacter americanus’ (CLam) and ‘Ca. Liberibacter asiaticus’ (CLas). However, there are few studies about HLB epidemiology when both Liberibacter spp. and its insect vector, the Asian citrus psyllid (ACP, Diaphorina citri), are present. The objective of this work was to compare the transmission of HLB by ACP when both CLam and CLas are present as primary inoculum. Two experiments were performed under screenhouse conditions from April 2008 to January 2012 (experiment 1) and from February 2011 to December 2015 (experiment 2). The experiments were carried out with sweet orange plants infected with CLam or CLas as inoculum source surrounded by sweet orange healthy plants. One hundred Liberibacter-free adult psyllids were monthly confined to the source of inoculum plants for 7 days with subsequent free movement inside the screenhouse. Fortnightly, nymphs and adults of psyllids were monitored. Psyllid and leaf samples were collected periodically for Liberibacter detection by PCR or quantitative PCR. CLas was detected more frequently than CLam in both psyllid and leaf samples. No mixed infections were detected in the psyllids. A clear prevalence of CLas over CLam was observed in both experiments. The final HLB incidences were 16.7 and 14.5% of Liberibacter-positive test plants, and CLas was detected in 92.3 and 93.1% of these infected plants. Mixed infection was observed only in 3.8% of infected test plants in experiment 1. These results endorse the shift in the prevalence of CLam to CLas observed in citrus orchards of São Paulo, Brazil.
Low-dose Droperidol Reduces the Amplitude of Transcranial Electrical Motor-evoked Potential: A Randomized, Double-blind, Placebo-controlled Trial
Authors: Mitsuma Yusuke , Furutani Kenta , Deguchi Hiroyuki , Kamiya Yoshinori , Tanaka Takahiro , Kitamura Nobutaka , Baba Hiroshi
Published: August 2021

Background:

Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes.

Methods:

Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range).

Results:

The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P<0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group.

Conclusions:

Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.
The Open Triradiate Cartilage: How Young Is Too Young for Total Hip Arthroplasty?
Authors: Rainer William , Shirley Matthew B. , Trousdale Robert T. , Shaughnessy William J.
Published: August 2021

Background:

There is, to our knowledge, no published literature regarding primary total hip arthroplasty (THA) in pediatric patients with an open triradiate cartilage. The purpose of this study was to report the outcomes following primary THA in pediatric patients with open triradiate cartilage at a single intuition.

Methods:

Using a single institution’s Total Joint Registry, 12 patients (13 hips) were identified as having undergone primary THA with open triradiate cartilage between the years of 2000 and 2019. The mean age and body mass index of this group were 13.1 years and 25.5 kg/m2, respectively. The cohort was composed of 10 males, and the mean follow up was 5.5 years. Indications for surgery, functional outcomes, and radiographic signs of stable fixation were analyzed.

Results:

The most common indication for surgery was avascular necrosis secondary to corticosteroid use (31%), followed by avascular necrosis after operative management of slipped capital femoral epiphysis (23%). The proportion of patients able to achieve independent, gait-aid free, ambulation improved from 23% to 100%. Mean postoperative Harris Hip Score was 92.3. All constructs were cementless, and bearing surfaces included ceramic-on-ceramic in 62% and ceramic on highly crosslinked polyethylene bearings in the remainder. Radiographic review at final follow up demonstrated osseointegration in 12 of 13 (92%) acetabular components. Although 1 patient experienced both acetabular component loosening and instability, on separate occasions, there were no incidences of infection, wound dehiscence, thromboembolic events, or failure secondary to wear.

Conclusions:

In this study, THA in patients with an open triradiate cartilage yielded significant clinical improvement, low complication rates and good initial implant survivorship at early follow up. Awaiting closure of the triradiate cartilage for concerns of decreased fixation and implant survivorship may be unnecessary.

Level of Evidence:

Level IV—case series.
Primary Bacterial Pyomyositis in Children: A Systematic Review
Authors: Vij Neeraj , Ranade Ashish S. , Kang Paul , Belthur Mohan V.
Published: August 2021

Background:

Tropical pyomyositis has had a recent increase in the United States, Europe, and other nontropical areas. The purpose of this study was to provide an accurate description of the demographics, presenting features, sites of involvement, microbiology, imaging modalities, medical and surgical management, complications, and predictors of clinical course.

Methods:

We searched PubMed, Cochrane, Web of Science Collection, Scopus, and Embase databases yielding 156 studies. Of these, 23 articles were selected for statistical analysis.

Results:

The average age at presentation was 8.4±1.9 years with males more commonly affected. Fever, painful limp, and localized pain were the most common presenting symptoms. Pelvis, lower extremity, trunk and spine, in descending order, were the most commonly affected locations. Iliopsoas, obturator musculature, and gluteus musculature were the most commonly affected muscle groups. The mean time to diagnosis was 6.6±3.05 days. Staphylococcus aureus was the most common offending organism. The mean length of hospital stay was 12.0±4.6 days. Medical management alone was successful in 40% of cases (143/361) with an average duration of 9.5±4.0 and 22.7±7.2 days of intravenous and oral antibiotics, respectively. Surgical management consisted of open drainage in 91.3% (199/218) or percutaneous drainage in 8.7% (19/218) of cases. Painful limp, fever, and larger values of white cell count and erythrocyte sedimentation rate were associated with an increased need for surgery. Obturator and calf muscle involvement were strongly associated with multifocal involvement. There were 42 complications in 41 patients (11.3%). Methicillin-resistant S. aureus was associated with an increased risk of complications. The most common complications were osteomyelitis, septicemia, and septic arthritis.

Conclusions:

Primary pyomyositis should be considered in cases suggesting pediatric infection. Magnetic resonance imaging is the most commonly used imaging modality; however, ultrasound is useful given its accessibility and low cost. Medical management alone can be successful, but surgical treatment is often needed. The prognosis is favorable. Early diagnosis, appropriate medical management, and potential surgical drainage are required for effective treatment.

Level of Evidence:

Level IV—systematic review.
Terminal Syme Amputation of the Great Toe in the Pediatric Population
Authors: Gibson Thomas W. , Westberry David E. , Carpenter Ashley M. , Colucciello Nicholas , Carson Lisa
Published: August 2021

Background:

In the pediatric population, chronic ingrown toenails (onychocryptosis) can cause infection (paronychia), debilitating pain, and may be unresponsive to conservative treatments. Following multiple failed interventions, a terminal Syme amputation is one option for definitive treatment of chronic onychocryptosis. This procedure involves amputation of the distal aspect of the distal phalanx of the great toe with complete removal of the nail bed and germinal center, preventing further nail growth and recurrence.

Methods:

A retrospective review was performed to determine outcomes of a terminal Syme amputation in the pediatric population. Inclusion criteria included treatment of onychocryptosis involving terminal Syme amputation with a minimum follow-up of 1 year. The medical record was reviewed to assess previous failed treatment efforts, perioperative complications, radiographic outcomes, and the need for additional procedures.

Results:

From 1984 to 2017, 11 patients (13 halluces) with onychocryptosis were treated with a terminal Syme amputation. There were no intraoperative complications. One hallux had a postoperative infection requiring antibiotics as well as partial nail regrowth following the terminal Syme procedure that required subsequent removal of the residual nail. Following partial nail ablation, the patient had no further nail growth. An additional patient also developed a postoperative infection requiring oral antibiotic treatment. All patients returned to full weight-bearing physical activities within 6 weeks of surgery.

Conclusions:

Terminal Syme amputation was successful in treating pediatric patients who have recalcitrant onychocryptosis and paronychia. There was little functional consequence following terminal Syme amputation of the great toe in this patient population, making it an effective salvage procedure.

Level of Evidence:

Level IV—retrospective comparative study.
Machine Learning Prediction of Death in Critically Ill Patients With Coronavirus Disease 2019
Authors: Churpek Matthew M. , Gupta Shruti , Spicer Alexandra B. , Hayek Salim S. , Srivastava Anand , Chan Lili , Melamed Michal L. , Brenner Samantha K. , Radbel Jared , Madhani-Lovely Farah , Bhatraju Pavan K. , Bansal Anip , Green Adam , Goyal Nitender , Shaefi Shahzad , Parikh Chirag R. , Semler Matthew W. , Leaf David E.
Published: August 2021

OBJECTIVES:

Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019.

DESIGN:

This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration.

SETTING:

Sixty-eight U.S. ICUs.

PATIENTS:

Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao
2/Fio
2 ratio were the most important predictors in the eXtreme Gradient Boosting model.

CONCLUSIONS:

eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.
Safety and Feasibility of an Interdisciplinary Treatment Approach to Optimize Recovery From Critical Coronavirus Disease 2019
Authors: Mayer Kirby P. , Parry Selina M. , Kalema Anna G. , Joshi Rajan R. , Soper Melissa K. , Steele Angela K. , Lusby Megan L. , Dupont-Versteegden Esther E. , Montgomery-Yates Ashley A. , Morris Peter E.
Published: August 2021

OBJECTIVES:

Examine the safety and feasibility of a multimodal in-person or telehealth treatment program, administered in acute recovery phase for patients surviving critical coronavirus disease 2019.

DESIGN:

Pragmatic, pre-post, nonrandomized controlled trial with patients electing enrollment into one of the two recovery pathways.

SETTING:

ICU Recovery Clinic in an academic medical center.

PATIENTS:

Adult patients surviving acute respiratory failure due to critical coronavirus disease 2019.

INTERVENTIONS:

Patients participated in combined ICU Recovery clinic and 8 weeks of physical rehabilitation delivered: 1) in-person or 2) telehealth. Patients received medical care by an ICU Recovery Clinic interdisciplinary team and physical rehabilitation focused on aerobic, resistance, and respiratory muscle training.

MEASUREMENTS AND MAIN RESULTS:

Thirty-two patients enrolled with mean age 57 ± 12, 62% were male, and the median Sequential Organ Failure Assessment score was 9.5. There were no differences between the two groups except patients in telehealth pathway (n = 10) lived further from clinic than face-to-face patients (162 ± 60 vs 31 ± 47 kilometers, t = 6.06, p < 0.001). Four safety events occurred: one minor adverse event in the telehealth group, two minor adverse events, and one major adverse event in the in-person group. Three patients did not complete the study (two in-person and one telehealth). Six-minute walk distance increased to 101 ± 91 meters from pre to post (n = 29, t = 6.93, p < 0.0001), which was similar between the two groups (110 vs 80 meters, t = 1.34, p = 0.19). Self-reported levels of anxiety, depression, and distress were high in both groups with similar self-report quality of life.

CONCLUSIONS:

A multimodal treatment program combining care from an interdisciplinary team in an ICU Recovery Clinic with physical rehabilitation is safe and feasible in patients surviving the ICU for coronavirus disease 2019 acute respiratory failure.
Age-dependent Radiation Dose Rates from Canine Sn-117m Treatments
Authors: Arno Matthew G. , Smith Chad
Published: August 2021

Tin-117 m (Sn-117m) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The decay process for Sn-117m is internal conversion wherein IC electrons and auger electrons provide the therapeutic effect. Additionally, the most prominent gamma emission is 158.6 keV. The effective dose rate received by a person interacting at close distances with a treated dog is needed to determine the person's total dose and thus regulatory compliance. Simple measurement of the dose rate at a given distance does not provide an accurate measurement of the effective dose to a person due to the non-uniform nature of the radiation field at close distances. MNCP models of the interactions of five ages of humans at three distances were created to determine the effective dose rates using the methodology from NRC Regulatory Guide 8.40. Ratios of the effective dose rate to the person to the measured dose rate at 1 m from the same source were calculated.
The Effect of Stepping Back From the X-Ray Table on Operator Radiation Exposure
Authors: Wilson Robert F. , Gainor John P. , Allen Blair
Published: August 2021

Background: Nearly all radiation safety courses teach that scatter radiation around the x-ray table falls with the inverse of the distance from the imaging site. Humans, however, are complex x-ray reflectors and the application of the inverse square law to clinical imaging is only assumed. Methods: We measured scatter radiation at two positions where staff commonly stand around the x-ray table. Using an anthropomorphic human phantom, human and pig cadavers, and a glass sphere, we measured scatter radiation levels in each position, and then 2- and 3-fold the distance from the imaging site. We compared the measured scatter radiation to that predicted by the common inverse square law and a more detailed geometric inverse square law. Results: In all but the glass sphere, scatter radiation was much higher below the table (68–74% of all scatter radiation, depending on model and position) than above the table (26–32% of scatter radiation, p < 0.01). Scatter radiation fell with increasing distance from the table, but above the table both inverse square laws significantly over-estimated the benefit of stepping back (19–93% overestimation by geometric inverse square law at 2-fold distance, 14–46% at 3-fold). In addition, a pelvis in the phantom appeared to cause significant scatter radiation field anomalies at the angiographer position. Conclusion: Stepping back from the table does not reduce scatter radiation levels as much as the inverse square law predicts. The geometric inverse square law best predicts the reduction in scatter radiation below the table, but above the table it too overestimates the benefit of stepping back. The irregularity of the scatter radiation field should be taken into account by scatter radiation shielding systems.
Ocular lymphoproliferative disorders
Authors: Moussa Kareem , Everett Lesley
Published: August 2021

Purpose of review

Ocular lymphoproliferative disorders are a heterogenous group of pathologic disorders with significant impact on quality of life and, at times, may be life-threatening. Due to the rarity of these disorders, information regarding proper diagnosis, treatment, and prognosis is limited. This review summarizes the key features of the unique diseases within this group of lymphoproliferative disorders, with a focus on disease presentation, diagnostic considerations, and treatment and prognosis.

Recent findings

High-quality data from recent studies have provided answers regarding clinical outcomes for subsets of ocular lymphoproliferative disorders and are included herein. New diagnostic techniques are also discussed as well as current treatment strategies.

Ocular lymphoproliferative disorders are a rare group of diseases. Key features of each disease is presented in this review in a concise and readable format, as well as updated information regarding diagnostic considerations and treatment options.
Safe Use of Propranolol in a Patient With PHACES Syndrome: A Case Report
Authors: Ferreira João Euzébio Encarnação , Ferreira Marina Vilela Chagas , Zatz Rafael , Foronda Gustavo , Gemperli Rolf , Goldenberg Dov Charles
Published: August 2021

Infantile hemangioma is the most common vascular tumor of childhood. Hemangiomas in a segmental facial distribution may be associated with structural brain, arterial, cardiac, or other malformations, components of PHACES syndrome. In this syndrome, the pharmacological treatment of hemangiomas that require systemic therapy is usually done with corticosteroids or beta-blockers. However, there have been some concerns regarding the use of beta-blockers for those patients with central nervous system arteriopathies. We herein report a case of a patient with PHACES syndrome, an extensive facial hemangioma and critical arterial malformation who was successfully treated with propranolol with no neurological or vascular complications.
Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound
Authors: Zhang Wenbin , Mintz Gary S. , Cao Yang , Matsumura Mitsuaki , Lee Tetsumin , Hoshino Masahiro , Usui Eisuke , Kanaji Yoshihisa , Murai Tadashi , Yonetsu Taishi , Kakuta Tsunekazu , Maehara Akiko
Published: August 2021

Objectives

We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients.

Methods

A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed.

Results

Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology.

Conclusion

Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.
Contemporary use of anticoagulation in the cardiac catheterization laboratory: a review
Authors: Klinkhammer Brent J. , Nathan Sandeep , Patel Ankitkumar K.
Published: August 2021

Anticoagulation during percutaneous coronary interventions has a rich history that has been shaped by several key clinical trials. The correct choice of anticoagulation during interventions can maximize patient outcomes and ensure a safe procedure. However, in some specific situations, anticoagulation may not be required at all. In this review article, we review the significant clinical trials and current guidelines regarding the use of anticoagulation in the catheterization laboratory and discuss the unique pharmacological aspects of the most commonly used agents, with an emphasis on the specific pharmacokinetic parameters that dictate how these agents are used and monitored. Finally, we discussed the future directions in anticoagulation therapy in coronary artery disease. This review serves as a robust synopsis of the clinical data for practicing clinicians and fellows in training.
Addiction Nursing Competencies
Authors: Wason Kristin , Potter Annie , Alves Justin , Loukas Vanessa L. , Lastimoso Charmaine , Sodder Shereen , Caputo Andrea , LaBelle Colleen T.
Published: August 2021

With the increased role of nurses in caring for patients with substance addiction, there was a clear need to develop the Addiction Nursing Competencies to guide and support the nursing workforce. A literature search revealed a lack of formal instruments to assess and guide nurses in caring for persons with substance use disorders. The Addiction Nursing Competencies were created using existing nursing education frameworks and addiction nurse care manager clinical guidelines.
Increased capsid oligomerization is deleterious to dengue virus particle production
Authors: Sangiambut Sutha , Promphet Natcha , Chaiyaloom Suwipa , Puttikhunt Chunya , Avirutnan Panisadee , Kasinrerk Watchara , Sittisombut Nopporn , Malasit Prida
Published: August 2021

The capsid protein (C) of dengue virus is required for viral infectivity as it packages viral RNA genome into infectious particles. C exists as a homodimer that forms via hydrophobic interactions between the α2 and α4 helices of monomers. To identify C region(s) important for virus particle production, a complementation system was employed in which single-round infectious particles are generated by trans-encapsidation of a viral C-deleted genome by recombinant C expressed in mosquito cells. Mutants harbouring a complete α3 deletion, or a dual Ile65-/Trp69-to-Ala substitution in the α3 helix, exhibited reduced production of infectious virus. Unexpectedly, higher proportions of oligomeric C were detected in cells expressing both mutated forms as compared with the wild-type counterpart, indicating that the α3 helix, through its internal hydrophobic residues, may down-modulate oligomerization of C during particle formation. Compared with wild-type C, the double Ile65-/Trp69 to Ala mutations appeared to hamper viral infectivity but not C and genomic RNA incorporation into the pseudo-infectious virus particles, suggesting that increased C oligomerization may impair DENV replication at the cell entry step.
Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia
Authors: Zhang Shiping , Yi Shuanglong , Wang Linfang , Li Shuhua , Wang Honglei , Song Li , Ou Jiayao , Zhang Min , Wang Ruiqi , Wang Mengxiao , Zheng Yuchen , Yang Kai , Liu Tong , Ho Margaret S.
Published: August 2021

Autophagy is a major means for the elimination of protein inclusions in neurons in neurodegenerative diseases such as Parkinson’s disease (PD). Yet, the mechanism of autophagy in the other brain cell type, glia, is less well characterized and remains largely unknown. Here we present evidence that the PD risk factor Cyclin G-associated kinase (GAK)/dAuxilin (dAux) is a new component in glial autophagy. GAK/dAux directly interacts with ULK1/Atg1 via its uncoating domain. Lack of GAK/dAux increases the autophagosome number and size in adult fly glia and mouse microglia, and generally upregulates levels of components in the initiation and PI3K class III complexes including ULK1/Atg1, demonstrating that GAK/dAux regulates the onset of glial autophagy. Consistently, lack of GAK/dAux enhances Atg1 and Atg9 trafficking to autophagosomes, promoting autophagy initiation. On the other hand, lack of GAK/dAux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/dAux might play additional roles in glial autophagy. Our findings identify a new autophagy factor in glia; considering the pivotal role of glia under pathological conditions, targeting glial autophagy is potentially a therapeutic strategy for PD.
Overexpression of HOP2 induces developmental defects and compromises growth in Arabidopsis
Authors: Garrido Ameth N. , Francom Therese , Divan Sakina , Kesserwan Mohamad , Daradur Jenya , Riggs C. Daniel
Published: August 2021

HOMOLOGOUS PAIRING 2 (HOP2) is a predominantly meiotic protein that plays a pivotal role in homologous chromosome pairing in organisms as diverse as yeast and mammals. While generating HOP2::GFP reporter lines, we identified two Arabidopsis T-DNA insertion mutants, stunted1 (std1) and stunted2 (std2) that exhibit pleiotropic phenotypes, including fasciated stems, altered phyllotaxy, floral organ defects, reduced fecundity, and an overall reduction in growth properties. TAIL-PCR followed by sequencing revealed several insertions near genes, but genotyping showed that none of the insertions are causal. Analysis the std mutants by qRT-PCR, and analysis of dexamethasone inducible HOP2 transgenic plants demonstrated that the std phenotypes are associated with ectopic/overexpression of HOP2. Based on the postulated mechanisms of HOP2 action, we speculate on how overexpression leads to these developmental/growth defects.
Epigenetic mechanisms of partial dosage compensation in an avian, female heterogametic system
Authors: Catalán Ana , Merondun Justin , Knief Ulrich , Wolf Jochen B.W.
Published: August 2021

The evolution of genetic sex determination is often accompanied by degradation of one of the proto sex chromosomes. Male heterogametic systems have evolved convergent, epigenetic mechanisms restoring the resulting imbalance in gene dosage between diploid autosomes (AA) and the hemizygous sex chromosome (X). Female heterogametic systems (AAfZWf, AAmZZm) tend to only show partial dosage compensation (0.5 < Zf:AAf< 1) and dosage balance (0.5<Zf:ZZm<1). The underlying mechanism remains largely elusive. Here, we quantified gene expression for a total of 15 male and female Eurasian crows (Corvus (corone) spp.) raised under common garden conditions. In addition, we characterized aspects of the regulatory landscape quantifying genome-wide ATAC-seq and 5mC methylation profiles. Partial dosage compensation was explained by female upregulation of Z-linked genes accompanied by increased chromatin accessibility on the female Z chromosome. 5mC methylation was strongly reduced in open chromatin-regions and GC islands and showed chromosome-, but no sex-specific variation. With the exception of the pseudo-autosomal region (PAR), female upregulation of gene expression was evenly spread across the Z chromosome without evidence for regional epigenetic regulation, as has for example been suggested for the male hypermethylated region (MHM) in chicken. Our results support the hypothesis that partial dosage compensation in female heterogametic systems is subject to chromosome-wide, epigenetic control mediated by differential chromatin accessibility between the sexes.
Functionally analogous body- and animacy-responsive areas in the dog (Canis familiaris) and human occipito-temporal lobe
Authors: Boch Magdalena , Wagner Isabella C. , Karl Sabrina , Huber Ludwig , Lamm Claus
Published: August 2021

Comparing the neural correlates of socio-cognitive skills across species provides insights into the evolution of the social brain and has revealed face- and body-sensitive regions in the primate temporal lobe. Although from a different lineage, dogs share convergent visuo-cognitive skills with humans and a temporal lobe which evolved independently in carnivores. We investigated the neural correlates of face and body perception in dogs (N= 15) and humans (N= 40) using functional MRI. Combining univariate and multivariate analysis approaches, we found functionally analogous occipito-temporal regions involved in the perception of animate entities and bodies in both species, while only humans had regions specialized for face perception. Though unpredicted, we also observed neural representations of faces compared to inanimate objects, and dog compared to human bodies in dog olfactory regions. These findings shed light on the evolutionary foundations of human and dog social cognition and the predominant role of the temporal lobe.
SKIOME Project: a curated collection of skin microbiome datasets enriched with study-related metadata
Authors: Agostinetto G. , Bozzi D. , Porro D. , Casiraghi M. , Labra M. , Bruno A.
Published: August 2021

Large amounts of data from microbiome-related studies have been (and are currently being) deposited on international public databases. These datasets represent a valuable resource for the microbiome research community and could serve future researchers interested in integrating multiple datasets into powerful meta-analyses. However, this huge amount of data lacks harmonization and is far from being completely exploited in its full potential to build a foundation that places microbiome research at the nexus of many subdisciplines within and beyond biology. Thus, urges the need for data accessibility and reusability, according to FAIR (Findable, Accessible, Interoperable, and Reusable) principles, as supported by National Microbiome Data Collaborative and FAIR Microbiome.

To tackle the challenge of accelerating discovery and advances in skin microbiome research, we collected, integrated and organized existing microbiome data resources from human skin 16S rRNA amplicon sequencing experiments. We generated a comprehensive collection of datasets, enriched in metadata, and organized this information into data frames ready to be integrated into microbiome research projects and advanced post-processing analysis, such as data science applications (e.g. machine learning). Furthermore, we have created a data retrieval and curation framework built on three different stages to maximize the retrieval of datasets and metadata associated with them. Lastly, we highlighted some caveats regarding metadata retrieval and suggested ways to improve future metadata submissions.

Overall, our work resulted in a curated skin microbiome datasets collection accompanied by a state-of-the-art analysis of the last 10 years of the skin microbiome field.
Nucleosome-directed replication origin licensing independent of a consensus DNA sequence
Authors: Li Sai , Wasserman Michael R. , Yurieva Olga , Bai Lu , O’Donnell Michael E. , Liu Shixin
Published: August 2021

The numerous enzymes and cofactors involved in eukaryotic DNA replication are conserved from yeast to human, and the budding yeast Saccharomyces cerevisiae (S.c.) has been a useful model organism for these studies. However, there is a gap in our knowledge of why replication origins in higher eukaryotes do not use a consensus DNA sequence as found in S.c.. Using in vitro reconstitution and single-molecule visualization, we show here that S.c. origin recognition complex (ORC) stably binds nucleosomes and that ORC-nucleosome complexes have the intrinsic ability to load the replicative helicase MCM double hexamers onto adjacent nucleosome-free DNA regardless of sequence. Furthermore, we find that Xenopus laevis nucleosomes can substitute for yeast ones in engaging with ORC. Combined with new analysis of genome-wide ORC binding, our results lead us to propose that the yeast origin recognition machinery contains the cryptic capacity to bind nucleosomes near a nucleosome-free region and license origins, and that this nucleosome-directed origin licensing paradigm generalizes to all eukaryotes.
Microbial loop of a Proterozoic ocean analogue
Authors: Saini Jaspreet S , Hassler Christel , Cable Rachel , Fourquez Marion , Danza Francesco , Roman Samuele , Tonolla Mauro , Storelli Nicola , Jacquet Stéphan , Zdobnov Evgeny M. , Duhaime Melissa B.
Published: August 2021

Meromictic Lake Cadagno, an ancient ocean analogue, is known for its permanent stratification and persistent anoxygenic microbial bloom within the chemocline. Although the anaerobic microbial ecology of the lake has been extensively studied for at least 25 years, a comprehensive picture of the microbial food web linking the bacterial layer to phytoplankton and viruses, with explicit measures of primary and secondary production, is still missing. This study sought to understand better the abundances and productivity of microbes in the context of nutrient biogeochemical cycling across the stratified zones of Lake Cadagno. Photosynthetic pigments and chloroplast 16S rRNA gene phylogenies suggested the presence of eukaryotic phytoplankton through the water column. Evidence supported high abundances of Ankyra judayi, a high-alpine adapted chlorophyte, in the oxic mixolimnion where oxygenic-primary production peaked. Through the low- and no-oxygen chemocline and monimolimnion, chlorophytes related to Closteriopsis acicularis, a known genus of meromictic lakes, and Parachlorella kessleri were observed. Chromatium, anoxygenic phototrophic sulfur bacteria, dominated the chemocline along with Lentimicrobium, a genus of known fermenters whose abundance was newly reported in Lake Cadagno. Secondary production peaked in the chemocline suggesting primary producers depend on heterotrophs for nutrient remineralization. As previously observed, sulfur-reducing bacteria (SRBs), especially Desulfocapsa and Desulfobulbus, were present in the chemocline and anoxic monimolimnion. Virus-to-microbe ratios (VMR) peaked in the zone of phytoplankton yet were at a minimum at the peak of Chromatium. These dynamic trends suggest viruses may play a role in the modulation of oxygenic and anoxygenic photo- and chemosynthesis in Lake Cadagno and other permanently stratified systems.

Importance

As a window to the past, the study offers insights into the role of microbial guilds of Proterozoic ocean chemoclines in the production and recycling of organic matter of sulfur- and ammonia-containing ancient oceans. The new observations described here suggest that eukaryotic algae were persistent in the low oxygen upper-chemocline in association with purple and green sulfur bacteria in the lower half of the chemocline. Further, this study provides the first insights into Lake Cadagno viral ecology. High viral abundances suggested viruses may be essential components of the chemocline where their activity may result in the release and recycling of organic matter. The framework developed in this study through the integration of diverse geochemical and biological data types lays the foundation for future studies to quantitatively resolve the processes performed by discrete populations comprising the microbial loop in this early anoxic ocean analogue.
Sorbitol in loquat promotes early flower bud differentiation via the MADS-box transcription factor EjCAL
Authors: Xu Hongxia , Chen Ting , Qi Meng , Li Xiaoying , Chen Junwei
Published: August 2021

The sugar alcohol sorbitol plays an important signaling role in fruit trees. Here, we found that sorbitol significantly increased during flower bud differentiation (FBD) in loquat (Eriobotrya japonica Lindl.) from the physiological FBD stage (EjS1) to the morphological FBD stage (EjS2), and it then decreased in the panicle development stage (EjS3) compared to in EjS2, and in subsequent stages. Spraying sorbitol increased the sorbitol content and thereby promoted early FBD and increased the proportion of flower buds that completed FBD. A transcriptomics analysis showed that the expression of a MADS-box transcription factor (TF) family gene, EjCAL, was highly correlated with the FBD phenotypic data. EjCAL-overexpressing transgenic tobacco exhibited the early FBD phenotype. Using the EjCAL promoter as bait in a yeast-one hybrid (Y1H) assay, the TF ERF12 was identified. Chromatin immunoprecipitation (ChIP)-PCR confirmed that EjERF12 can bind to the EjCAL promoter, and β-glucuronidase (GUS) activity assays demonstrated that EjERF12 can regulate EjCAL expression. Spraying loquat with sorbitol confirmed that EjERF12 and EjCAL expression were regulated by sorbitol. We also identified downstream functional genes (EjUF3GaT1, EjGEF2, and EjADF1) that might be involved in FBD. Finally, we found that the change in the level of hyperoside (a reproduction-related flavonoid) was consistent with that of sorbitol during FBD in loquat, and EjCAL can bind to the EjUF3GaT1 promoter and might thereby regulate hyperoside biosynthesis. Two early- and late-flowering varieties of loquat and EjCAL-overexpressing transgenic tobacco plants were used to confirm this hypothesis.

One-sentence summary

Sorbitol promotes bud differentiation via EjCAL.
IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity
Authors: Schick Judith , Lacorcia Matthew , Altunay Meltem , Schubart Christoph , Bodendorfer Barbara , Christensen Dennis , Alexander Christian , Wirtz Stefan , Vöhringer David , da Costa Clarissa Prazeres , Lang Roland
Published: August 2021

The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6-dimycolate (TDM). Recently, we found that IL-4 down-regulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis. Here, we investigated functional consequences of IL-4 and helminth infection on MINCLE-driven macrophage activation and Th1/Th17 adjuvanticity. IL-4 inhibited MINCLE and cytokine induction after macrophage infection withMycobacterium bovisBacille Calmette-Guerin (BCG). Infection of mice with BCG upregulated MINCLE on myeloid cells, which was inhibited by IL-4 plasmid injection and by infection with the nematodeNippostrongylus brasiliensisin monocytes. To determine the impact of helminth infection on MINCLE-dependent immune responses, we vaccinated mice with a recombinant protein together with the MINCLE ligand Trehalose-6,6-dibehenate (TDB) as adjuvant. Concurrent infection withN. brasiliensisor withSchistosoma mansonipromoted T cell-derived IL-4 production and suppressed Th1/Th17 differentiation in the spleen. In contrast, helminth infection did not reduce Th1/Th17 induction by TDB in draining peripheral lymph nodes, where IL-4 levels were unaltered. Upon use of the TLR4-dependent adjuvant G3D6A,N. brasiliensisinfection impaired selectively the induction of splenic antigen-specific Th1 but not of Th17 cells. Thus, helminth infection attenuated the Th17 response to MINCLE-dependent immunization in an organ-specific manner. Taken together, our results demonstrate down-regulation of MINCLE expression on monocytes and macrophages by IL-4 as a possible mechanism of thwarted Th17 vaccination responses by underlying helminth infection.
Broad phylogenetic and functional diversity among mixotrophic consumers of Prochlorococcus
Authors: Li Qian , Edwards Kyle F. , Schvarcz Christopher R. , Steward Grieg F.
Published: August 2021

Small eukaryotic phytoplankton are major contributors to global primary production and marine biogeochemical cycles. Many taxa are thought to be mixotrophic, but quantitative studies of phagotrophy exist for very few. In addition, little is known about consumers of Prochlorococcus, the abundant cyanobacterium at the base of oligotrophic ocean food webs. Here we describe thirty-nine new phytoplankton isolates from the North Pacific Subtropical Gyre (Station ALOHA), all flagellates ∼2–5 um diameter, and we quantify their ability to graze Prochlorococcus. The mixotrophs are from diverse classes (dictyochophytes, haptophytes, chrysophytes, bolidophytes, a dinoflagellate, and a chlorarachniophyte), many from previously uncultured clades. Grazing ability varied substantially, with specific clearance rate (volume cleared per body volume) varying over ten-fold across isolates and six-fold across genera. Slower grazers tend to create more biovolume per prey biovolume consumed. Using qPCR we found that the haptophyte Chrysochromulina was most abundant among the isolated mixotrophs at Station ALOHA, with 76–250 cells mL-1 across depths in the upper euphotic zone. Our results show that within a single ecosystem the phototrophs that ingest bacteria come from many branches of the eukaryotic tree, and are functionally diverse, indicating a broad range of strategies along the spectrum from phototrophy to phagotrophy.