bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes
Authors: Green Sabrina I , Clark Justin R , Santos Haroldo H , Weesner Kyle E , Salazar Keiko C , Aslam Saima , Campbell J William , Doernberg Sarah B , Blodget Emily , Morris Michele I , Suh Gina A , Obeid Karam , Silveira Fernanda P , Filippov Andrey A , Whiteson Katrine L , Trautner Barbara W , Terwilliger Austen L , Maresso Anthony
Published: June 2023

Background

Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

Methods

We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration–approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded.

Results

Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported.

Conclusions

Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.
Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda
Authors: Ericson Jessica E , Burgoine Kathy , Kumbakumba Elias , Ochora Moses , Hehnly Christine , Bajunirwe Francis , Bazira Joel , Fronterre Claudio , Hagmann Cornelia , Kulkarni Abhaya V , Kumar M Senthil , Magombe Joshua , Mbabazi-Kabachelor Edith , Morton Sarah U , Movassagh Mercedeh , Mugamba John , Mulondo Ronald , Natukwatsa Davis , Kaaya Brian Nsubuga , Olupot-Olupot Peter , Onen Justin , Sheldon Kathryn , Smith Jasmine , Ssentongo Paddy , Ssenyonga Peter , Warf Benjamin , Wegoye Emmanuel , Zhang Lijun , Kiwanuka Julius , Paulson Joseph N , Broach James R , Schiff Steven J
Published: June 2023

Background

Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis.

Methods

We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes.

Results

Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus.

Conclusions

Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.
Long-term Real-world Protection Afforded by Third mRNA Doses Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections, Coronavirus Disease 19-related Emergency Attendances and Hospitalizations Amongst Older Singaporeans During an Omicron XBB Wave
Authors: Wee Liang En , Pang Deanette , Chiew Calvin , Tan Janice , Lee Vernon , Ong Benjamin , Lye David Chien , Tan Kelvin Bryan
Published: June 2023

Background

Literature on long-term real-world vaccine effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccines (up to and beyond 360 days) is scarce. We report estimates of protection against symptomatic infection, emergency department (ED) attendances and hospitalizations up to and beyond 360 days post-receipt of booster messenger RNA (mRNA) vaccines among Singaporeans aged ≥60 years during an Omicron XBB wave.

Methods

We conducted a population-based cohort study including all Singaporeans aged ≥60 years with no documented prior SARS-CoV-2 infection who had previously received ≥3 doses of mRNA vaccines (BNT162b2/mRNA-1273), over a 4-month period during transmission of Omicron XBB. We reported the adjusted incidence-rate-ratio (IRR) for symptomatic infections, ED attendances and hospitalizations at different time-intervals from both first and second boosters, using Poisson regression; with the reference group being those who received their first booster 90 to 179 days prior.

Results

In total, 506 856 boosted adults were included, contributing 55 846 165 person-days of observation. Protection against symptomatic infections among those who received a third vaccine dose (first booster) waned after 180 days with increasing adjusted IRRs; however, protection against ED attendances and hospitalizations held up, with comparable adjusted IRRs with increasing time from third vaccine doses (≥360 days from third dose: adjusted IRR [ED attendances] = 0.73, 95% confidence interval [CI] = .62–.85; adjusted IRR [hospitalization] = 0.58, 95% CI = .49–.70).

Conclusions

Our results highlight the benefit of a booster dose in reducing ED attendances and hospitalizations amongst older adults aged ≥60 years with no documented prior SARS-CoV-2 infection, during an Omicron XBB wave; up to and beyond 360 days post-booster. A second booster provided further reduction.
Urinary single-cell sequence analysis of the urinary macrophage in different outcomes of membranous nephropathy
Authors: Liu Xi , Zhao Yu , Niu Yangyang , Xie Qionghong , Nie Hao , Jin Yun , Zhang Yingying , Lu Yuqiu , Zhu Saiya , Zuo Wei , Yu Chen
Published: June 2023

Background

Great progress has been made in the diagnosis and treatment of membranous nephropathy (MN). However, a significant number of patients do not respond to immunosuppressive therapy and eventually progress to end-stage kidney disease. To investigate the mechanism of different outcome of MN, we performed single-cell sequencing to analyze the urine cells of patients with and without complete remission of MN.

Methods

Urine single-cell RNA sequencing was performed on 12 healthy controls (HC) and 15 patients with MN. The patients were divided into a complete remission group (CR, n = 9) and a no remission group (NR, n = 6).

Results

(i) Macrophages were the largest group in urine cells, comprising 48.02%, 68.96% and 20.95% in the HC, CR and NR groups, respectively. (ii) Urinary macrophages expressing FIColin-1 and S100 calcium-binding protein A8 were mainly found in the HC and CR groups, indicating that they were derived from bone marrow and peripheral blood, while the urinary macrophages expressing the regulator of G-protein signaling 1 (RGS1) and HLA-DPA1, mainly found in the NR group, were derived from renal resident macrophages. (iii) In healthy adults, urine macrophages expressed the metallothionein family, indicating that they can regulate anti-inflammatory and proinflammatory functions bidirectionally. In the CR group, the urine macrophages showed strong proinflammatory properties. In the NR group, the urinary macrophages mainly associated with the level of proteinuria and the impaired renal function.

Conclusions

Our study firstly delineated the differences in urinary cell maps between healthy individuals and MN patients with CR or NR outcomes. Not only the origin but also the function of urine macrophages were different in the HC, CR and NR groups.
A Novel Enzymatic Hydrolysis Method for Urine Aldosterone Quantification: A Case for Reassessing Clinical Cut-Offs of Primary Aldosteronism
Authors: Yazdanpanah Mehrdad , Delaney Sarah R , Beriault Daniel R
Published: June 2023

Background

Primary aldosteronism (PA) is a common endocrine cause of secondary hypertension. The aldosterone/renin ratio is an important tool for PA screening, and dynamic testing in serum or urine is used to confirm the diagnosis. While LC-MS/MS is considered the gold standard for testing, there is significant interlaboratory variability between the extraction procedures, which can impact diagnostic interpretation. To help overcome this, we present a simple and accurate LC-MS/MS method for the quantification of both serum and urine aldosterone using a novel enzymatic hydrolysis procedure.

Methods

Serum and urine aldosterone was extracted and measured by LC-MS/MS. Urine-conjugated aldosterone glucuronide was hydrolyzed using a genetically modified glucuronidase enzyme. The assay precision, accuracy, limit of quantification, recovery, and carryover were evaluated and the new assay cut-offs were proposed.

Results

The liquid chromatography method allowed for adequate separation of the aldosterone peak from closely eluting peaks. Significant in vitro aldosterone loss was observed during acid-catalyzed hydrolysis of urine, which was corrected with the addition of the internal standard to the urine before the hydrolysis step. Glucuronidase catalyzed hydrolysis of urine aldosterone glucuronide displays good correlation with the corrected acid-catalyzed hydrolysis. Serum aldosterone showed good agreement with reference values and the consensus range reported for external quality assessment specimens.

Conclusion

A simple, fast, and highly accurate method for the detection of serum and urine aldosterone has been developed. The proposed novel enzymatic procedure allows for short hydrolysis time and compensates for urine aldosterone loss during the hydrolysis step.
Assessing stress physiology within a conservation breeding program for an endangered species
Authors: Falconer S , McAdie M , Mastromonaco G , Schulte-Hostedde A I
Published: June 2023

Conservation breeding programs typically involve the management of individuals both in and ex situ, so it is vital to understand how the physiology of managed species changes in these environments to maximize program outcomes. The Vancouver Island marmot (VIM; Marmota vancouverensis) is one species that has been managed in a conservation breeding program to recover the critically low wild population. Previous research has shown there are differences in hair glucocorticoid concentrations for VIMs in different managed groups in the program. Therefore, we used >1000 blood samples collected since the program’s inception to assess the neutrophil to lymphocyte (N:L) ratio among captive, pre-release, post-release and wild populations as another metric of stress. In situ VIM populations were found to have a significantly higher N:L ratio than ex situ populations, suggesting that the wild is a more physiologically challenging environment than managed care. Moreover, the effect of age, sex and the month of sampling on the N:L ratio were found to be different for each population. Age had the greatest magnitude of effect in the wild population, and sex was only significant in ex situ populations. This study provided previously unknown insights into the physiology of VIMs and increased post-release monitoring will be useful in the future to fully understand how physiology may be contributing to differences in survival of VIMs in the program.
Shakespeare and Plautus: exploring metrical influence
Authors: Christensen Alexander
Published: June 2023

Scholars have recognized for some time that Shakespeare’s early comedies drew much from Plautine comedy. Although these points of influence have long been established, discussion of Plautus’ influence on Shakespeare has not often moved beyond them to broader questions of whether he had any influence over Shakespeare’s tragedies, over his later career in general, or over more specific techniques of playwriting, like characterization or metrical composition. This article takes up these latter two issues. I argue that Shakespeare’s use of metrical variation in his most sympathetic characters’ soliloquies correlates closely with Plautus’ practice of using polymetric songs to introduce his most sympathetic characters. As examples, I analyse Shakespeare’s Hamlet and Plautus’ Trinummus. Though no conclusive evidence can be found to prove that Shakespeare digested Plautus’ metrics in addition to his comic plots, the article suggests that Plautus’ influence on Shakespeare could run deeper than previously thought.
Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes
Authors: Tang Chaojun , Chen Guona , Wu Fan , Cao Yiren , Yang Fei , You Tao , Liu Chu , Li Menglu , Hu Shuhong , Ren Lijie , Lu Qiongyu , Deng Wei , Xu Ying , Wang Guixue , Jo Hanjoong , Zhang Yonghong , Wu Yi , Zabel Brian A , Zhu Li
Published: June 2023

Aims

Chemoattractants and their cognate receptors are essential for leucocyte recruitment during atherogenesis, and atherosclerotic plaques preferentially occur at predilection sites of the arterial wall with disturbed flow (d-flow). In profiling the endothelial expression of atypical chemoattractant receptors (ACKRs), we found that Ackr5 (CCRL2) was up-regulated in an endothelial subpopulation by atherosclerotic stimulation. We therefore investigated the role of CCRL2 and its ligand chemerin in atherosclerosis and the underlying mechanism.

Methods and results

By analysing scRNA-seq data of the left carotid artery under d-flow and scRNA-seq datasets GSE131776 of ApoE−/− mice from the Gene Expression Omnibus database, we found that CCRL2 was up-regulated in one subpopulation of endothelial cells in response to d-flow stimulation and atherosclerosis. Using CCRL2−/−ApoE−/− mice, we showed that CCRL2 deficiency protected against plaque formation primarily in the d-flow areas of the aortic arch in ApoE−/− mice fed high-fat diet. Disturbed flow induced the expression of vascular endothelial CCRL2, recruiting chemerin, which caused leucocyte adhesion to the endothelium. Surprisingly, instead of binding to monocytic CMKLR1, chemerin was found to activate β2 integrin, enhancing ERK1/2 phosphorylation and monocyte adhesion. Moreover, chemerin was found to have protein disulfide isomerase-like enzymatic activity, which was responsible for the interaction of chemerin with β2 integrin, as identified by a Di-E-GSSG assay and a proximity ligation assay. For clinical relevance, relatively high serum levels of chemerin were found in patients with acute atherothrombotic stroke compared to healthy individuals.

Conclusions

Our findings indicate that d-flow-induced CCRL2 promotes atherosclerotic plaque formation via a novel CCRL2-chemerin-β2 integrin axis, providing potential targets for the prevention or therapeutic intervention of atherosclerosis.
IHM-DB: a curated collection of metagenomics data from the Indian Himalayan Region, and automated pipeline for 16S rRNA amplicon-based analysis (AutoQii2)
Authors: Khatri Abhishek , Thakur Aman , Lepcha Ayush , Acharya Vishal , Kumar Rakshak
Published: June 2023

Indian Himalayan metagenome database (IHM-DB) is a web-based database consisting of information on metagenomic datasets from various databases and publications that are specifically reported from the Indian Himalayan Region (IHR). The online interface allows users to view or download the dataset-specific information for the respective states, category-wise, or according to the hypervariable region. The IHM-DB also provides an opportunity for the users to access the metagenomic publications from the IHR as well as upload their microbiome information to the website. Additionally, an open-source 16S rRNA amplicon-based automated bioinformatics pipeline, AutoQii2, allows users to analyze the single-end and paired-end raw reads. AutoQii2 provides an automated approach for performing analysis such as quality check, adapter and chimera removal and exploits the latest ribosomal database project classifier for taxonomic assignments. The source code of the AutoQii2 pipeline is available at https://gitlab.com/khatriabhi2319/autoqii2.

Database URL https://ham.ihbt.res.in/ihmdb and https://fgcsl.ihbt.res.in/ihmdb
Impact of frailty on hiatal hernia repair: a nationwide analysis of in-hospital clinical and healthcare utilization outcomes
Authors: Lee Y , Huo B , McKechnie T , Agzarian J , Hong D
Published: June 2023

Previous studies recommend a watch-and-wait approach to paraesophageal hernia (PEH) repair due to an increased risk for mortality. While contemporary studies suggest that elective surgery is safe and effective, many patients presenting with PEH are elderly. Therefore, we assessed the impact of frailty on in-hospital outcomes and healthcare utilization among patients receiving PEH repair. This retrospective population-based cohort study assessed patients from the National Inpatient Sample database who received PEH repair between October 2015 to December 2019. Demographic and perioperative data were gathered, and frailty was measured using the 11-item modified frailty index. The outcomes measured were in-hospital mortality, complications, discharge disposition, and healthcare utilization. Overall, 10,716 patients receiving PEH repair were identified, including 1442 frail patients. Frail patients were less often female and were more often in the lowest income quartile compared to robust patients. Frail patients were at greater odds for in-hospital mortality [odds ratio (OR) 2.83 (95% CI 1.65–4.83); P < 0.001], postoperative ICU admissions [OR 2.07 (95% CI 1.55–2.78); P < 0.001], any complications [OR 2.18 (95% CI 1.55–2.78); P < 0.001], hospital length of stay [mean difference (MD) 1.75 days (95% CI 1.30–2.210; P < 0.001], and total admission costs [MD $5631.65 (95% CI $3300.06–$7.963.24); P < 0.001] relative to their robust patients. While PEH repair in elderly patients is safe and effective, frail patients have an increased rate of in-hospital mortality, postoperative ICU admissions, complications, and total admission costs. Clinicians should consider patient frailty when identifying the most appropriate surgical candidates for PEH repair.
Does surgical companionship modify the learning curve for fenestrated and branched endovascular aortic repair?
Authors: Mesnard Thomas , Jeanneau Clément , Patterson Benjamin O , Dubosq Maxime , Vidal-Diez Alberto , Haulon Stéphan , Sobocinski Jonathan
Published: June 2023

OBJECTIVES

The goal of this study was to describe the learning curve of an operator trained in an aortic centre during the first years of performing fenestrated/branched endovascular aortic repairs independently.

METHODS

Patients electively treated with fenestrated/branched stent grafts from January 2013 to March 2020 were included retrospectively. Groups were defined according to the treating operator: experienced operator (group 1), early-career operator (group 2) or both during a 14-month surgical companionship period (group 3). The early-career operator’s learning curve was assessed using a cumulative sum analysis. A composite criterion including technical failure, death and/or any major adverse event was evaluated in a logistic regression model.

RESULTS

Overall, 437 patients (93% male; median 69 (63, 77) years old) were included (group 1: n = 240; group 2: n = 173; group 3: n = 24). There were significantly more extended thoraco-abdominal aneurysms (extent I, II, III and V) in group 1 compared to group 2 [n = 68 (28%) vs 19 (11%), P<0.001]. The technical success rate was 94% (P=0.874). The 30-day mortality and/or major adverse event rates in juxta-/pararenal aneurysms or extent IV thoraco-abdominal aneurysms were 8.1% in group 1 and 9.7% in group 2 (P = 0.612), whereas they were 10% (group 1) and 0 (group 2) for extended thoraco-abdominal aneurysms (P=0.339). The adjusted cumulative sum analysis highlighted satisfactory results from the beginning of the experience. The operator’s experience was not predictive of the composite criterion [adjusted OR 0.77; 95% (0.42, 1.40); P=0.40].

CONCLUSIONS

This study demonstrated favourable outcomes in patients treated with a fenestrated/branched aortic stent graft performed by an early-career operator trained in a high-volume centre from the beginning of independent practice.
The impact of surgical learning curve on short-term outcomes after bilateral lung transplantation: results from a multidisciplinary surgical team
Authors: Chou Pin-Li , Liu Kuo-Sheng , Chao Yin-Kai , Wen Yu-Wen , Liu Yun-Hen , Hsieh Ming-Ju , Chiu Chien-Hung , Fang Hsin-Yueh , Cheng Chia-Hui , Hu Han-Chung , Chen Wei-Hsun
Published: June 2023

OBJECTIVES

The aim of this study was to examine the impact of surgical learning curve on short-term clinical outcomes of patients after bilateral lung transplantation (LTx) performed by a surgical multidisciplinary team (MDT).

METHODS

Forty-two patients underwent double LTx from December 2016 to October 2021. All procedures were performed by a surgical MDT in a newly established LTx program. The time required for bronchial, left atrial cuff and pulmonary artery anastomoses was the main end point to assess surgical proficiency. The associations between the surgeon’s experience and procedural duration were examined by linear regression analysis. We employed the simple moving average technique to generate learning curves and evaluated short-term outcomes before and after achieving surgical proficiency.

RESULTS

Both total operating time and total anastomosis time were inversely associated with the surgeon’s experience. On analysing the learning curve for bronchial, left atrial cuff and pulmonary artery anastomoses using moving averages, the inflection points occurred at 20, 15 and 10 cases, respectively. To assess the learning curve effect, the study cohort was divided into early (cases 1–20) and late (cases 21–42) groups. Short-term outcomes—including intensive care unit stay, in-hospital stay and severe complications—were significantly more favourable in the late group. Furthermore, there was a notable tendency for patients in the late group to experience a decreased duration of mechanical ventilation along with reduced instances of grade 3 primary graft dysfunction.

CONCLUSIONS

A surgical MDT can perform double LTx safely after 20 procedures.
Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure: a nationwide Danish study
Authors: Skibsted Christian Valdemar , Korsholm Kasper , Pedersen Lars , Bonnesen Kasper , Nielsen-Kudsk Jens Erik , Schmidt Morten
Published: June 2023

Aims

Transcatheter closure of patent foramen ovale (PFO) is the recommended stroke prevention treatment in patients ≤60 years with cryptogenic ischemic stroke and PFO. Atrial fibrillation or flutter (AF) is a known potential procedure-related complication, but long-term risk of developing AF remains unknown. This paper studied the long-term risk of developing AF following PFO closure.

Methods and results

A Danish nationwide cohort study was conducted. During 2008–2020, this study identified a PFO closure cohort, a PFO diagnosis cohort without PFO closure, and a general population comparison cohort matched 10:1 to the PFO closure cohort on age and sex. The outcome was first-time AF diagnosis. Risk of AF and multivariable-adjusted hazard ratio (HR) of the association between PFO closure or PFO diagnosis and AF were calculated. A total of 817 patients with PFO closure, 1224 with PFO diagnosis, and 8170 matched individuals were identified. The 5 year risk of AF was 7.8% [95% confidence interval (CI): 5.5–10] in the PFO closure cohort, 3.1% (95% CI: 2.0–4.2) in the PFO diagnosis cohort, and 1.2% (95% CI: 0.8–1.6) in the matched cohort. The HR of AF comparing PFO closure with PFO diagnosis was 2.3 (95% CI: 1.3–4.0) within the first 3 months and 0.7 (95% CI: 0.3–1.7) thereafter. The HR of AF comparing PFO closure with the matched cohort was 51 (95% CI: 21–125) within the first 3 months and 2.5 (95% CI: 1.2–5.0) thereafter.

Conclusion

Patent foramen ovale closure was not associated with any substantial increased long-term risk of developing AF beyond the well-known procedure-related short-term risk.
Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing
Authors: Pujol-López Margarida , Ferró Elisenda , Borràs Roger , Garre Paz , Guasch Eduard , Jiménez-Arjona Rafael , Garcia-Ribas Cora , Doltra Adelina , Niebla Mireia , Carro Esther , Roca-Luque Ivo , Guichard J Baptiste , Puente J Luis , Uribe Laura , Vázquez-Calvo Sara , Castel M Ángeles , Arbelo Elena , Porta-Sánchez Andreu , Sitges Marta , Tolosana José M , Mont Lluís
Published: June 2023

Aims

To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking.

Methods and results

A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP.

Conclusion

Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).
Unusual case of pernicious anaemia masquerading as thrombotic thrombocytopenic purpura in the setting of multiple normal vitamin B12 deficiency parameters: preventing anchoring and overdiagnosis
Authors: Mohammad Zoya , Ananthaneni Anil , Fontenot Andee , Ramadas Poornima , Nour Salloum Mohammad
Published: June 2023

Background

Pseudo-thrombotic microangiopathy (pseudo- thrombotic microangiopathy (TMA)) is a rare presentation of B12 deficiency. Overlapping features like elevated LDH/total bilirubin with low haemoglobin/haptoglobin/platelets could deceivingly suggest thrombotic thrombocytopenic purpura (TTP) resulting in avoidable procedures/treatments.

Case presentation

A 36-year-old female with hypothyroidism initially presented to clinic with fatigue, palpitations, lightheadedness, and dyspnoea over a 3-month duration and was found to have a haemoglobin of 5.7 g/dL. She received two packed red blood cell units in the emergency room and subsequently discharged with outpatient follow-up and empiric oral iron. During her follow-up visit, she was found to have easy bruisability, gum bleeding, and generalized weakness from hemolytic anaemia (mean corpuscular volume (MCV) 90 fL, haptoglobin <8 mg/dL, LDH >4,000 U/L and schistocytosis on CBC) and thrombocytopenia of 52 K/uL. Due to PLASMIC score of 6 and suspicion for TTP, she was transferred to our facility and tr eated with three cycles of plasma exchange and prednisone but were discontinued when ADAMTS13 levels returned normal. While the patient had normal B12 levels, further testing revealed positive intrinsic factor antibodies (IF-Ab) and an elevated MMA level of 1.56 umol/L. Replacement with cobalamin led to normalization of labs and symptoms.

Conclusions

Timely diagnosis of pseudo-TMA was exceptionally challenging due to several overlapping features with TTP including normal B12 and normal MCV. B12 levels may falsely appear normal in pernicious anemia due to IF-Ab interference with chemiluminescent immunoassay. Schistocytes lower the MCV in automated cell counters. Lower reticulocyte index (<2%), presence of immature/large platelets and teardrop cells, elevated MMA and a higher LDH (>2500) are indicative of B12 deficiency.
Spatial patterns in host-associated and free-living bacterial communities across six temperate estuaries
Authors: Suzzi Alessandra L , Stat Michael , Gaston Troy F , Huggett Megan J
Published: June 2023

A major goal of microbial ecology is to establish the importance of spatial and environmental factors in driving community variation. Their relative importance likely varies across spatial scales, but focus has primarily been on free-living communities within well-connected aquatic environments rather than less connected island-like habitats such as estuaries, and key host-associated communities within these systems. Here we sampled both free-living (seawater and sediment) and host-associated (estuarine fish hindgut microbiome, Pelates sexlineatus) communities across six temperate Australian estuaries spanning ∼500 km. We find that spatial and environmental factors have different influences on these communities, with seawater demonstrating strong distance-decay relationships (R = -0.69) and significant associations with a range of environmental variables. Distance-decay relationships were weak for sediment communities but became stronger over smaller spatial scales (within estuaries, R = -0.5) potentially reflecting environmental filtering across biogeochemical gradients or stochastic processes within estuary sediments. Finally, P. sexlineatus hindgut microbiome communities displayed weak distance-decay relationships (R = -0.36) and limited variation explained by environmental variables, indicating the significance of host-related factors in driving community variation. Our findings provide important ecological insights into the spatial distributions and driving forces of both free-living and host-associated bacterial patterns across temperate estuarine systems.
The Evolutionary Constraints on Angiosperm Chloroplast Adaptation
Authors: Robbins Elizabeth H J , Kelly Steven
Published: June 2023

The chloroplast (plastid) arose via the endosymbiosis of a photosynthetic cyanobacterium by a nonphotosynthetic eukaryotic cell ∼1.5 billion years ago. Although the plastid underwent rapid evolution by genome reduction, its rate of molecular evolution is low and its genome organization is highly conserved. Here, we investigate the factors that have constrained the rate of molecular evolution of protein-coding genes in the plastid genome. Through phylogenomic analysis of 773 angiosperm plastid genomes, we show that there is substantial variation in the rate of molecular evolution between genes. We demonstrate that the distance of a plastid gene from the likely origin of replication influences the rate at which it has evolved, consistent with time and distance-dependent nucleotide mutation gradients. In addition, we show that the amino acid composition of a gene product constraints its substitution tolerance, limiting its mutation landscape and its corresponding rate of molecular evolution. Finally, we demonstrate that the mRNA abundance of a gene is a key factor in determining its rate of molecular evolution, suggesting an interaction between transcription and DNA repair in the plastid. Collectively, we show that the location, the composition, and the expression of a plastid gene can account for >50% of the variation in its rate of molecular evolution. Thus, these three factors have exerted a substantial limitation on the capacity for adaptive evolution in plastid-encoded genes and ultimately constrained the evolvability of the chloroplast.
Reduced histone gene copy number disrupts Drosophila Polycomb function
Authors: McPherson Jeanne-Marie E , Grossmann Lucy C , Salzler Harmony R , Armstrong Robin L , Kwon Esther , Matera A Gregory , McKay Daniel J , Duronio Robert J
Published: June 2023

The chromatin of animal cells contains two types of histones: canonical histones that are expressed during S phase of the cell cycle to package the newly replicated genome, and variant histones with specialized functions that are expressed throughout the cell cycle and in non-proliferating cells. Determining whether and how canonical and variant histones cooperate to regulate genome function is integral to understanding how chromatin-based processes affect normal and pathological development. Here, we demonstrate that variant histone H3.3 is essential for Drosophila development only when canonical histone gene copy number is reduced, suggesting that coordination between canonical H3.2 and variant H3.3 expression is necessary to provide sufficient H3 protein for normal genome function. To identify genes that depend upon, or are involved in, this coordinate regulation we screened for heterozygous chromosome 3 deficiencies that impair development of flies bearing reduced H3.2 and H3.3 gene copy number. We identified two regions of chromosome 3 that conferred this phenotype, one of which contains the Polycomb gene, which is necessary for establishing domains of facultative chromatin that repress master regulator genes during development. We further found that reduction in Polycomb dosage decreases viability of animals with no H3.3 gene copies. Moreover, heterozygous Polycomb mutations result in de-repression of the Polycomb target gene Ubx and cause ectopic sex combs when either canonical or variant H3 gene copy number is reduced. We conclude that Polycomb-mediated facultative heterochromatin function is compromised when canonical and variant H3 gene copy number falls below a critical threshold.
Phenotype switching of the mutation rate facilitates adaptive evolution
Authors: Lobinska Gabriela , Pilpel Yitzhak , Ram Yoav
Published: June 2023

The mutation rate plays an important role in adaptive evolution. It can be modified by mutator and anti-mutator alleles. Recent empirical evidence hints that the mutation rate may vary among genetically identical individuals: evidence from bacteria suggests that the mutation rate can be affected by expression noise of a DNA repair protein and potentially also by translation errors in various proteins. Importantly, this non-genetic variation may be heritable via a transgenerational epigenetic mode of inheritance, giving rise to a mutator phenotype that is independent from mutator alleles. Here, we investigate mathematically how the rate of adaptive evolution is affected by the rate of mutation rate phenotype switching. We model an asexual population with two mutation rate phenotypes, non-mutator and mutator. An offspring may switch from its parental phenotype to the other phenotype. We find that switching rates that correspond to so-far empirically described non-genetic systems of inheritance of the mutation rate lead to higher rates of adaptation on both artificial and natural fitness landscapes. These switching rates can maintain within the same individuals both a mutator phenotype and intermediary mutations, a combination that facilitates adaptation. Moreover, non-genetic inheritance increases the proportion of mutators in the population, which in turn increases the probability of hitchhiking of the mutator phenotype with adaptive mutations. This in turns facilitates the acquisition of additional adaptive mutations. Our results rationalize recently observed noise in the expression of proteins that affect the mutation rate and suggest that non-genetic inheritance of this phenotype may facilitate evolutionary adaptive processes.
The Movement Deviation Profile Can Differentiate Faller and Non-Faller Older Adults
Authors: Júlio Cíntia Elord , Antonialli Fernanda Colella , Nascimento Tamara Medeiros do , Sá Karina Araújo , Barton Gábor József , Lucareli Paulo Roberto Garcia
Published: June 2023

Background

The World Health Organization considers falls the second leading cause of death by accidental injury worldwide and one of the most frequent complications in older adults during activities of daily living. Several tasks related to fall risk have been individually assessed describing kinematic changes in older adults. The study proposal was to identify which functional task differentiates faller and non-faller older adults using the movement deviation profile (MDP).

Methods

This cross-sectional study recruited 68 older adults aged ≥60 years by convenience sampling. Older adults were divided into 2 groups: with and without a history of falls (34 older adults in each group). The MDP analyzed the 3-dimensional angular kinematics data of tasks (ie, gait, walking turn, stair ascent and descent, sit-to-stand, and stand-to-sit), and the Z score of the mean MDP identified which task presented the greatest difference between fallers and non-fallers. A multivariate analysis with Bonferroni post hoc verified the interaction between groups considering angular kinematic data and the cycle time of the task. Statistical significance was set at 5% (p < .05).

Results

Z score of the MDPmean showed an interaction between groups (λ = 0.67, F = 5.085, p < .0001). Fallers differed significantly from non-fallers in all tasks and the greatest difference was in stair descent (Z score = 0.89). The time to complete each task was not different between groups.

Conclusions

The MDP distinguished older adult fallers from non-fallers. The stair descent task should be highlighted because it presented the greatest difference between groups.
Have Middle-Aged and Older Americans Become Lonelier? 20-Year Trends From the Health and Retirement Study
Authors: Surkalim Daniel L , Clare Philip J , Eres Robert , Gebel Klaus , Bauman Adrian , Ding Ding
Published: June 2023

Objectives

Despite media and public dialog portraying loneliness as a worsening problem, little is known about how the prevalence of loneliness has changed over time. Our study aims to identify (a) temporal trends in episodic and sustained loneliness (lonely in 1 wave vs consistently lonely in 3 consecutive waves); (b) trends across sociodemographic subgroups by sex, race/ethnicity, birth cohort, education, employment status, marital status, and living alone; and (c) longitudinal predictors of loneliness in middle-aged and older Americans (≥50 years).

Methods

Based on Waves 3 (1996) to 14 (2018) of the Health and Retirement Study (n = 18,841–23,227), we conducted a series of lagged mixed-effects Poisson regression models to assess trends of episodic and sustained loneliness in the overall and sociodemographic subgroup samples (by sex, race/ethnicity, birth cohort, education, employment, relationship, and living alone status). To examine the predictors of episodic and sustained loneliness, we used a multivariate mixed-effects Poisson regression model with all sociodemographic variables entered into the same model.

Results

Episodic loneliness prevalence decreased from 20.1% to 15.5% and sustained loneliness from 4.6% to 3.6%. Trends were similar across most subgroups. Males, Caucasians, those born in 1928–1945, with university education, working, married/partnered, and those not living alone reported lower episodic and sustained loneliness, although associations with sustained loneliness were stronger.

Discussion

Contrary to common perceptions, loneliness has decreased over 20 years of follow-up in middle-aged and older Americans. Several sociodemographic subgroups have been identified as having a higher risk of loneliness, prompting targeted public health attention.
Method for estimating azimuthal intensity distribution of microtremors using simple arrays
Authors: Kimura Harusato , Tomobe Haruka , Morikawa Hitoshi
Published: June 2023

In this paper, a method is proposed for estimating the intensity distribution of microtremors for the arrival direction, from simultaneous observations of vertical motion, using an array of simple geometry consisting of only three receivers. This method is based on the fact that the complex coherence function, which is defined as the normalized cross-spectrum of microtremor recordings observed at two sites, contains information about the azimuthal intensity distribution of the microtremor field. To obtain the azimuthal intensity distribution from a limited number of conditions, the functional form of the azimuthal intensity distribution of the microtremor field was assumed and its parameters were estimated. Information on the arrival direction of the microtremor field was specifically obtained using particle swarm optimization (PSO), one of the metaheuristic methods, and then employed to identify the parameters. The proposed method was applied to ideal synthetic data to clarify the potential problems that may arise from using PSO as the core algorithm. Despite PSO-induced errors, the proposed method was able to accurately infer directional information over a wide frequency range. The proposed method was also applied to actual field data to verify its effectiveness and applicability. The results indicate that the proposed method can provide similar results to the frequency–wavenumber (FK) method in a wide frequency range. The quasi-FK spectrum, an effective mode representation of the FK spectrum, was displayed to visualize the directionality.
Impact of vascular screening interventions on perceived threat, efficacy beliefs and behavioural intentions: a systematic narrative review
Authors: Anokye Reindolf , Jackson Ben , Dimmock James , Dickson Joanne M , Kennedy Mary A , Schultz Carl J , Blekkenhorst Lauren C , Hodgson Jonathan M , Stanley Mandy , Lewis Joshua R
Published: June 2023

Health-related behaviours contribute to the global burden of cardiovascular disease (CVD). Cardiovascular imaging can be used to screen asymptomatic individuals for increased risk of CVD to enable earlier interventions to promote health-related behaviours to prevent or reduce CVD risk. Some theories of behaviour and behaviour change assume that engagement in a given behaviour is a function of individual threat appraisals, beliefs regarding the performance of behaviour, self-efficacy for performing the desired behaviour and/or dispositions to act (e.g. behavioural intentions). To date, little is known about the impact of cardiovascular imaging interventions on these constructs. This article summarises evidence related to perceived threat, efficacy beliefs, and behavioural intentions after CVD screening. We identified 10 studies (2 RCTs and 8 non-randomised studies, n = 2498) through a combination of screening citations from published systematic reviews and meta-analyses and searching electronic databases. Of these, 7 measured behavioural intentions and perceived susceptibility and 3 measured efficacy beliefs. Findings showed largely encouraging effects of screening interventions on bolstering self-efficacy beliefs and strengthening behavioural intentions. Imaging results that suggest the presence of coronary or carotid artery disease also increased perceived susceptibility to CVD. However, the review also identified some gaps in the literature, such as a lack of guiding theoretical frameworks and assessments of critical determinants of health-related behaviours. By carefully considering the key issues highlighted in this review, we can make significant strides towards reducing CVD risks and improving population health.
Is inadequate health literacy associated with worse health outcomes among Chinese individuals with depression?
Authors: Mo Phoenix K H , Xie Luyao , Mak Winnie W S
Published: June 2023

Inadequate health literacy is a risk factor for poorer outcomes across various conditions. The present study examined the level of health literacy, as measured by the Single Item Literacy Screener (SILS), and its association with a range of physical and mental outcomes [e.g. health-related quality of life, depression, anxiety, well-being, body mass index (BMI)] among individuals with depression in Hong Kong. A total of 112 individuals with depression were recruited from the community and invited to complete a survey. Among the participants, 42.9% of them were classified as having inadequate health literacy as screened by the SILS. After adjusting for significant sociodemographic and background variables, participants with inadequate health literacy had significantly poorer health-related quality of life and well-being, and had higher scores in depression, anxiety and BMI compared with those with adequate health literacy. Inadequate health literacy was associated with a range of negative physical and mental outcomes among individuals with depression. Interventions promoting the health literacy level of individuals with depression are highly warranted.
Perspectives of youth in Ireland on school-based mental health and suicide prevention: the MYSTORY study
Authors: Walsh Eibhlin H , Herring Matthew P , McMahon Jennifer
Published: June 2023

Anxiety, depression, and suicide are leading causes of disability and death among young people, globally. Schools are an ideal setting to target young people’s mental health, yet young people’s beliefs about and experiences with school mental health and suicide prevention are not well understood. This gap in knowledge contradicts both national and international youth mental health recommendations and the United Nations Convention on the Rights of the Child, which collectively advocate for understanding young people’s perspectives on matters concerning them, including school mental health. Therefore, the Mental Health of Youth Story (MYSTORY) study explored young people’s perspectives on school mental health and suicide prevention using a participatory-based approach incorporating photovoice. MYSTORY consisted of a community/university partnership involving young people as participants (n = 14) and advisors (n = 6). Experiential, reflexive thematic analysis (TA) within a critical approach generated three themes relating to young people’s experiences with and beliefs about school mental health promotion and suicide prevention. Findings highlight the critical role of schools in impacting young people’s mental health, with the need to amplify youth voice and involvement in school mental health evident. Our study addresses an important gap by employing participatory-based approaches to explore young people’s perspectives on school mental health and suicide prevention. This is the first known study to explore young people’s perspectives on their voice and involvement in school mental health. Findings have important implications for youth and school mental health and suicide prevention research, policy, and practice.