bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycoproteomic and proteomic analysis of
Burkholderia cenocepacia
reveals glycosylation events within FliF and MotB are dispensable for motility
Authors: Lewis Jessica M. , Jebeli Leila , Coulon Pauline M. L. , Lay Catrina E. , Scott Nichollas E. 
Published: May 2024

ABSTRACT

Across the Burkholderia genus
O
-linked protein glycosylation is highly conserved. While the inhibition of glycosylation has been shown to be detrimental for virulence in
Burkholderia cepacia
complex species, such as
Burkholderia cenocepacia
, little is known about how specific glycosylation sites impact protein functionality. Within this study, we sought to improve our understanding of the breadth, dynamics, and requirement for glycosylation across the
B. cenocepacia O-
glycoproteome. Assessing the
B. cenocepacia
glycoproteome across different culture media using complementary glycoproteomic approaches, we increase the known glycoproteome to 141 glycoproteins. Leveraging this repertoire of glycoproteins, we quantitively assessed the glycoproteome of
B. cenocepacia
using Data-Independent Acquisition (DIA) revealing the
B. cenocepacia
glycoproteome is largely stable across conditions with most glycoproteins constitutively expressed. Examination of how the absence of glycosylation impacts the glycoproteome reveals that the protein abundance of only five glycoproteins (BCAL1086, BCAL2974, BCAL0525, BCAM0505, and BCAL0127) are altered by the loss of glycosylation. Assessing Δ
fliF
(ΔBCAL0525), Δ
motB
(ΔBCAL0127), and ΔBCAM0505 strains, we demonstrate the loss of FliF, and to a lesser extent MotB, mirror the proteomic effects observed in the absence of glycosylation in Δ
pglL
. While both MotB and FliF are essential for motility, we find loss of glycosylation sites in MotB or FliF does not impact motility supporting these sites are dispensable for function. Combined this work broadens our understanding of the
B. cenocepacia
glycoproteome supporting that the loss of glycoproteins in the absence of glycosylation is not an indicator of the requirement for glycosylation for protein function.

IMPORTANCE

Burkholderia cenocepacia
is an opportunistic pathogen of concern within the Cystic Fibrosis community. Despite a greater appreciation of the unique physiology of
B. cenocepacia
gained over the last 20 years a complete understanding of the proteome and especially the O-glycoproteome, is lacking. In this study, we utilize systems biology approaches to expand the known
B. cenocepacia
glycoproteome as well as track the dynamics of glycoproteins across growth phases, culturing media and in response to the loss of glycosylation. We show that the glycoproteome of
B. cenocepacia
is largely stable across conditions and that the loss of glycosylation only impacts five glycoproteins including the motility associated proteins FliF and MotB. Examination of MotB and FliF shows, while these proteins are essential for motility, glycosylation is dispensable. Combined this work supports that
B. cenocepacia
glycosylation can be dispensable for protein function and may influence protein properties beyond stability.
Burden and frequency of viral testing of kidney and non-kidney transplant recipients
Authors: Kapoor Hema , Bi Caixia , Kroll Martin H. , Salm Ann E. , Dominguez Edward A. 
Published: May 2024

ABSTRACT

Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein–Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines.

IMPORTANCE

Guidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a
strategic plan
to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.
Basal erosion during the initiation of continental deep subduction in the North Qaidam ultrahigh-pressure metamorphic belt (NW China): Constraints from geochemistry and geochronology on eclogites and gneisses in the Chachahe unit
Authors: Ren Yunfei , Chen Danling , Zhu Xiaohui , Wang Haijie , Bai Bowen 
Published: May 2024

Abstract
Subduction erosion is thought to be a common process in active continental margins that removes upper-plate material and transfers it to the subduction channel. The North Qaidam ultrahigh-pressure metamorphic belt of NW China was formed by subduction of the Qaidam Block beneath the Quanji Block in the early Paleozoic. In this study, we found gneisses and eclogites in the Chachahe unit of the North Qaidam ultrahigh-pressure metamorphic belt that recorded 2.39–2.28 Ga magmatism and 1.93–1.87 Ga amphibolite-facies metamorphism prior to the early Paleozoic (452–439 Ma) eclogite-facies metamorphism. The Paleoproterozoic tectono-thermal history recorded by these gneisses and eclogites is distinct from that of the Qaidam Block but similar to that of the Quanji Block. The rock assemblages, field occurrences, geochemical characteristics, and zircon Lu-Hf isotopic compositions of these rocks closely resemble those of gneisses and enclosed mafic enclaves in the Delingha Complex in the basement of the Quanji Block and the mafic dikes intruded within it. This evidence clearly illustrates that the protoliths of gneisses and eclogites in the Chachahe unit were from the basement of the upper Quanji Block rather than the subducted Qaidam Block. Further considering the spatial location of the Chachahe unit, as well as similarities in early Paleozoic metamorphic ages, peak metamorphic conditions, and clockwise P-T paths between rocks in the Chachahe unit and those that originated from the Qaidam Block, we propose that the bottom basement of the Quanji Block was scraped off by basal erosion during the initiation of continental subduction, transported to mantle depth, and then exhumed with other slices from the subducted slab.
Associations of quantitative contrast sensitivity with vascular metrics on widefield swept-source OCT angiography across stages of diabetic retinopathy
Authors: Vingopoulos Filippos , Baldwin Grace , Katz Raviv , Cui Ying , Moon Jade Y , Garg Itika , Zeng Rebecca , Patel Nimesh A , Wu David , Husain Deeba , Miller Joan W , Kim Leo A , Vavvas Demetrios G , Miller John B 
Published: May 2024

PurposeTo investigate structure–function associations between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics across stages of non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR), without diabetic macular oedema.MethodsProspective cross-sectional study in 140 eyes of 99 patients: 33 mild NPDR, 24 moderate/severe NPDR, 15 PDR, 33 diabetic without DR (DMnoDR) and 46 control eyes. Mixed-effects multivariable regression models to evaluate associations between quantitative contrast sensitivity function (Adaptive Sensory Technology) and vessel density (VD) and vessel skeletonised density (VSD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) on same-day imaging with WF SS-OCTA (Plex Elite 9000, Carl Zeiss Meditec).ResultsStandardised β coefficients for area under the logarithm of contrast sensitivity function curve (AULCSF) versus visual acuity (VA) at 3×3 mm scans: SCP VSD (β=0.32, p<0.001 vs −0.18, p=0.044), DCP VSD (β=0.30, p<0.001 vs −0.21, p=0.02), SCP VD (β=0.25, p=0.004 vs −0.13, p=0.129), DCP VD (β=0.26, p=0.003 vs −0.19, p=0.034). AULCSF was significantly reduced in mild NPDR (β=−0.28, p<0.001) and DMnoDR (β=−0.19, p=0.005) versus controls, while VA was not significantly different. AULCSF performed better than VA in differentiating between controls and DMnoDR (0.69 vs 0.50), controls and mild NPDR (0.76 vs 0.61) and controls and moderate/severe NPDR (0.89 vs 0.73).ConclusionsDR-induced microvascular changes on OCTA are associated with larger changes on CS than in VA. CS is affected earlier than VA in the course of DR and performed better in discriminating between controls, DMnoDR and across DR stages.
Feasibility of multiorgan risk prediction with routinely collected diagnostics: a prospective cohort study in the UK Biobank
Authors: McCracken Celeste , Raisi-Estabragh Zahra , Szabo Liliana , Veldsman Michele , Raman Betty , Topiwala Anya , Roca-Fern�ndez Adriana , Husain Masud , Petersen Steffen E , Neubauer Stefan , Nichols Thomas E 
Published: May 2024

Objectives
Despite rising rates of multimorbidity, existing risk assessment tools are mostly limited to a single outcome of interest. This study tests the feasibility of producing multiple disease risk estimates with at least 70% discrimination (area under the receiver operating curve, AUROC) within the time and information constraints of the existing primary care health check framework.

Design
Observational prospective cohort study

Setting
UK Biobank.

Participants
228 240 adults from the UK population.

Interventions
None.

Main outcome measures
Myocardial infarction, atrial fibrillation, heart failure, stroke, all-cause dementia, chronic kidney disease, fatty liver disease, alcoholic liver disease, liver cirrhosis and liver failure.

Results
Using a set of predictors easily gathered at the standard primary care health check (such as the National Health Service Health Check), we demonstrate that it is feasible to simultaneously produce risk estimates for multiple disease outcomes with AUROC of 70% or greater. These predictors can be entered once into a single form and produce risk scores for stroke (AUROC 0.727, 95% CI 0.713 to 0.740), all-cause dementia (0.823, 95% CI 0.810 to 0.836), myocardial infarction (0.785, 95% CI 0.775 to 0.795), atrial fibrillation (0.777, 95% CI 0.768 to 0.785), heart failure (0.828, 95% CI 0.818 to 0.838), chronic kidney disease (0.774, 95% CI 0.765 to 0.783), fatty liver disease (0.766, 95% CI 0.753 to 0.779), alcoholic liver disease (0.864, 95% CI 0.835 to 0.894), liver cirrhosis (0.763, 95% CI 0.734 to 0.793) and liver failure (0.746, 95% CI 0.695 to 0.796).

Conclusions
Easily collected diagnostics can be used to assess 10-year risk across multiple disease outcomes, without the need for specialist computing or invasive biomarkers. Such an approach could increase the utility of existing data and place multiorgan risk information at the fingertips of primary care providers, thus creating opportunities for longer-term multimorbidity prevention. Additional work is needed to validate whether these findings would hold in a larger, more representative cohort outside the UK Biobank.
Challenges in reducing maternal and neonatal mortality in Niger: an in-depth case study
Authors: Kante Almamy Malick , Youssoufa Lamou Ousseini , Mounkaila Aida , Mahamadou Yahaha , Bamogo Assanatou , Jiwani Safia S , Hazel Elizabeth , Maïga Abdoulaye , Munos Melinda Kay , Walton Shelley , Tam Yvonne , Walker Neff , Akseer Nadia , Jue Wong Heather , Moussa Mohamed , Dagobi Abdoua Elhadji , Jessani Nasreen S , Amouzou Agbessi 
Published: May 2024

IntroductionRecent modelled estimates suggest that Niger made progress in maternal mortality since 2000. However, neonatal mortality has not declined since 2012 and maternal mortality estimates were based on limited data. We researched the drivers of progress and challenges.MethodsWe reviewed two decades of health policies, analysed mortality trends from United Nations data and six national household surveys between 1998 and 2021 and assessed coverage and inequalities of maternal and newborn health indicators. Quality of care was evaluated from health facility surveys in 2015 and 2019 and emergency obstetric assessments in 2011 and 2017. We determined the impact of intervention coverage on maternal and neonatal lives saved between 2000 and 2020. We interviewed 31 key informants to understand the factors underpinning policy implementation.ResultsEmpirical maternal mortality ratio declined from 709 to 520 per 100 000 live births during 2000–2011, while neonatal mortality rate declined from 46 to 23 per 1000 live births during 2000–2012 then increased to 43 in 2018. Inequalities in neonatal mortality were reduced across socioeconomic and demographic strata. Key maternal and newborn health indicators improved over 2000–2012, except for caesarean sections, although the overall levels were low. Interventions delivered during childbirth saved most maternal and newborn lives. Progress came from health centre expansion, emergency care and the 2006 fee exemptions policy. During the past decade, challenges included expansion of emergency care, continued high fertility, security issues, financing and health workforce. Social determinants saw minimal change.ConclusionsNiger reduced maternal and neonatal mortality during 2000–2012, but progress has stalled. Further reductions require strategies targeting comprehensive care, referrals, quality of care, fertility reduction, social determinants and improved security nationwide.
Comprehensive genomic filtering algorithm to expose the cause of skewed X chromosome inactivation. The proof of concept in female haemophilia expression
Authors: Ziegler Betiana Michelle , Abelleyro Miguel Martin , Marchione Vanina Daniela , Lazarte Nicolás , Ledesma Martín Manuel , Elhelou Ludmila , Neme Daniela , Rossetti Liliana Carmen , Medina-Acosta Enrique , Giliberto Florencia , De Brasi Carlos , Radic Claudia Pamela 
Published: May 2024

BackgroundExploring the expression of X linked disorders like haemophilia A (HA) in females involves understanding the balance achieved through X chromosome inactivation (XCI). Skewed XCI (SXCI) may be involved in symptomatic HA carriers. We aimed to develop an approach for dissecting the specific cause of SXCI and verify its value in HA.MethodsA family involving three females (two symptomatic with severe/moderate HA: I.2, the mother, and II.1, the daughter; one asymptomatic: II.2) and two related affected males (I.1, the father and I.3, the maternal uncle) was studied. The genetic analysis includedF8mutational screening, multiplex ligation-dependent probe amplification, SNP microarray, whole exome sequencing (WES) and Sanger sequencing. XCI patterns were assessed in ectoderm/endoderm and mesoderm-derived tissues usingAR-based andRP2-based systems.ResultsThe comprehensive family analysis identifies I.2 female patient as a heterozygous carrier ofF8:p.(Ser1414Ter) excluding copy number variations. A consistent XCI pattern of 99.5% across various tissues was observed. A comprehensive filtering algorithm for WES data was designed, developed and applied to I.2. A Gly58Arg missense variant inVMA21was revealed as the cause for SXCI.Each step of the variant filtering system takes advantage of publicly available genomic databases, non-SXCI controls and case-specific molecular data, and aligns with established concepts in the theoretical background of SXCI.ConclusionThis study acts as a proof of concept for our genomic filtering algorithm’s clinical utility in analysing X linked disorders. Our findings clarify the molecular aspects of SXCI and improve genetic diagnostics and counselling for families with X linked diseases like HA.
Analgesic benefits of regional anesthesia in the perioperative management of transition-related surgery: a systematic review
Authors: Katsnelson Glen , Brenna Connor T A , Girón-Arango Laura , Abdallah Yasmeen M , Brull Richard 
Published: May 2024

IntroductionTransition-related surgery is an effective treatment for gender dysphoria, but the perioperative analgesic management of transgender patients is nuanced and potentially complicated by higher rates of mood and substance use disorders. Regional anesthetic techniques are known to reduce pain severity and opioid requirements; however, little is known regarding the relative analgesic effectiveness of regional anesthesia for transgender patients undergoing transition-related surgery.MethodsWe performed a systematic review of the literature to evaluate original reports characterizing the analgesic effectiveness of regional anesthetic techniques for patients undergoing chest and/or genital transition-related surgery. Our primary outcomes were pain severity and opioid requirements on the first postoperative day.ResultsOf the 1863 records identified, 10 met criteria for inclusion and narrative synthesis. These included two randomized controlled trials, three cohort studies, and five case reports/series, comprising 293 patients. Four reports described 243 patients undergoing chest surgery, of whom 86% were transgender men undergoing mastectomy with pectoralis nerve blocks or local anesthetic instillation devices. The remaining six reports comprised 50 patients undergoing genital surgery, of whom 56% were transgender women undergoing vaginoplasty with erector spinae plane blocks or epidural anesthesia. Three studies directly compared regional techniques to parenteral analgesia alone. Two of these studies reported lower pain scores and opioid requirements on the first postoperative day with nerve blocks compared with none while the third study reported no difference between groups. Complications related to regional anesthetic techniques were rare among patients undergoing transition-related surgery.DiscussionDespite the ever-growing demand for transition-related surgery, the relative analgesic effectiveness of regional anesthesia for transgender patients undergoing transition-related surgery is very understudied and insufficient to guide clinical practice. Our systematic review of the literature serves to underscore regional anesthesia for transition-related surgery as a priority area for future research.
Cross-Seal IDE Trial: Prospective, Multicenter, Single-Arm Study of the Cross-Seal Suture-Mediated Vascular Closure Device System
Authors: Krishnan Prakash , Farhan Serdar , Zidar Frank , Krajcer Zvonimir , Metzger Christopher , Kapadia Samir , Moore Erin , Nazif Tamim , Garland Ty , Zhang Ming , Khera Sahil , Sharafuddin Mel , Patel Virendra I. , Bacharach John Michael , Coady Paul , Schermerhorn Marc L. , Shames Murray L. , Rahimi Saum , Panneton Jean M. , Elkins Craig , Foteh Mazin 
Published: May 2024

BACKGROUND:
An increasing number of interventional procedures require large-sheath technology (>12F) with a favorable outcome with endovascular rather than open surgical access. However, vascular complications are a limitation for the management of these patients. This trial aimed to determine the effectiveness and safety of the Cross-Seal suture-mediated vascular closure device in obtaining hemostasis at the target limb access site following interventional procedures using 8F to 18F procedural sheaths.

METHODS:
The Cross-Seal IDE trial (Investigational Device Exemption) was a prospective, single-arm, multicenter study in subjects undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheaths. The primary efficacy end point was time to hemostasis at the target limb access site. The primary safety end point was freedom from major complications of the target limb access site within 30 days post procedure.

RESULTS:
A total of 147 subjects were enrolled between August 9, 2019, and March 12, 2020. Transcatheter aortic valve replacement was performed in 53.7% (79/147) and percutaneous endovascular abdominal/thoracic aortic aneurysm repair in 46.3% (68/147) of subjects. The mean sheath ID was 15.5±1.8 mm. The primary effectiveness end point of time to hemostasis was 0.4±1.4 minutes. An adjunctive intervention was required in 9.2% (13/142) of subjects, of which 2.1% (3/142) were surgical and 5.6% (8/142) endovascular. Technical success was achieved in 92.3% (131/142) of subjects. Freedom from major complications of the target limb access site was 94.3% (83/88).

CONCLUSIONS:
In selected patients undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheath, Cross-Seal suture-mediated vascular closure device achieved favorable effectiveness and safety in the closure of the large-bore arteriotomy.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03756558.