bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction with the carboxy-terminal tip of SSB is critical for RecG function in E. coli
Authors: Bonde Nina J , Henry Camille , Wood Elizabeth A , Cox Michael M , Keck James L
Published: March 2023

In Escherichia coli, the single-stranded DNA-binding protein (SSB) acts as a genome maintenance organizational hub by interacting with multiple DNA metabolism proteins. Many SSB-interacting proteins (SIPs) form complexes with SSB by docking onto its carboxy-terminal tip (SSB-Ct). An alternative interaction mode in which SIPs bind to PxxP motifs within an intrinsically-disordered linker (IDL) in SSB has been proposed for the RecG DNA helicase and other SIPs. Here, RecG binding to SSB and SSB peptides was measured in vitro and the RecG/SSB interface was identified. The results show that RecG binds directly and specifically to the SSB-Ct, and not the IDL, through an evolutionarily conserved binding site in the RecG helicase domain. Mutations that block RecG binding to SSB sensitize E. coli to DNA damaging agents and induce the SOS DNA-damage response, indicating formation of the RecG/SSB complex is important in vivo. The broader role of the SSB IDL is also investigated. E. coli ssb mutant strains encoding SSB IDL deletion variants lacking all PxxP motifs retain wildtype growth and DNA repair properties, demonstrating that the SSB PxxP motifs are not major contributors to SSB cellular functions.
Colorful hues: insight into the mechanisms of anthocyanin pigmentation in fruit
Authors: Zhao Yun , Sun Juanli , Cherono Sylvia , An Jian-Ping , Allan Andrew C , Han Yuepeng
Published: March 2023

Anthocyanin is a vital indicator for both fruit nutritional and commercial value. Anthocyanin accumulation is a surprisingly complicated process mediated by multiple networks associated with genetic, developmental, hormonal, and environmental factors. Transcriptional regulation along with epigenetic regulation constitutes the dominant molecular framework for anthocyanin biosynthesis. Here, we focus on current knowledge on regulatory mechanisms of anthocyanin accumulation, with emphasis on the latest progress in transcriptional and epigenetic regulation and the crosstalk between various signaling pathways. We present an emerging picture of how various internal and external stimuli control anthocyanin biosynthesis. Additionally, we discuss the synergistic or antagonistic effect of developmental, hormonal and environmental cues on anthocyanin accumulation in fruit.
High-sensitivity cardiac troponin T in infants exposed to anti-Ro antibodies
Authors: Barsalou Julie , Jaeggi Edgar , Grosse-Wortmann Lars , Laskin Carl A , Adeli Khosrow , Silverman Earl D
Published: March 2023

Objectives

Cardiac involvement in neonatal lupus erythematosis (NLE) can present as myocarditis/endocardial fibroelastosis (EFE). It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) is useful in identifying subclinical myocardial inflammation in infants exposed prenatally to anti-Ro antibodies. This study reports hs-cTnT levels in infants exposed to anti-Ro antibodies with/without cardiac NLE and reports cardiac MRI (CMR) findings in a subset of these children.

Methods

The study included 45 consecutive infants exposed prenatally to anti-Ro antibodies with (n = 7) or without (n = 38) cardiac NLE, who were seen at the SickKids NLE Clinic between 2012 and 2014. Hs-cTnT levels were measured at least once, and those infants with values of ≥30 ng/l were offered the opportunity to undergo CMR. Descriptive statistics were performed.

Results

Of 38 infants without cardiac NLE, 25 had a hs-cTnT level of ≥30 ng/l (including 1 of >113 ng/l); of these, 8 underwent CMR (all without myocarditis/EFE). All 7 infants with cardiac NLE had at least one hs-cTnT level of ≥30 ng/l, but only 2/7 had a level of >113 ng/l; 4/7 infants with cardiac NLE had CMR (all without myocarditis/EFE); 6/7 infants with cardiac NLE had their steroid treatment adjusted based on the trend in their hs-cTnT levels.

Conclusion

Only 3/45 anti-Ro antibodies–exposed infants had hs-cTnT values outside the reference range reported in healthy infants. None of 12 infants who had CMR had subclinical myocarditis/EFE. Routine measurement of hs-cTnT in every anti-Ro antibody–exposed infant is not indicated. Further studies are needed to define the role of hs-cTnT as a biomarker for cardiac NLE.
Pulmonary and neurological health effects associated with exposure to representative composite manufacturing emissions and corresponding alterations in circulating metabolite profiles
Authors: Xia Li , Noh Yoorae , Whelton Andrew J , Boor Brandon E , Cooper Bruce , Lichti Nathanael I , Park Jae Hong , Shannahan Jonathan H
Published: March 2023

Cured-in-place pipe (CIPP) technology is increasingly being utilized to repair aging and damaged pipes, however, there are concerns associated with the public health hazards of emissions. CIPP installation involves the manufacture of a new plastic composite pipe at the worksite and includes multiple variable components including resin material, curing methods, and operational conditions. We hypothesize styrene-based composite manufacturing emissions (CMEs) will induce greater pulmonary inflammatory responses and oxidative stress, as well as neurological toxicity compared with nonstyrene CMEs. Further, these CME-toxicological responses will be sex- and time-dependent. To test the hypothesis, representative CMEs were generated using a laboratory curing chamber and characterized using thermal desorption-gas chromatography-mass spectrometry and photoionization detector. Styrene was released during staying, isothermal curing, and cooling phases of the process and peaked during the cooling phase. Male and female C57BL6/J mice were utilized to examine alterations in pulmonary responses and neurotoxicity 1 day and 7 days following exposure to air (controls), nonstyrene-CMEs, or styrene-CMEs. Serum styrene metabolites were increased in mice exposed to styrene-CMEs. Metabolic and lipid profiling revealed alterations related to CIPP emissions that were resin-, time-, and sex-dependent. Exposure to styrene-CMEs resulted in an influx of lymphocytes in both sexes. Expression of inflammatory and oxidative stress markers, including Tnfα, Vcam1, Ccl2, Cxcl2, Il6, Cxcl1, Tgfβ1, Tgmt2, and Hmox1, displayed alterations following exposure to emissions. These changes in pulmonary and neurological markers of toxicity were dependent on resin type, sex, and time. Overall, this study demonstrates resin-specific differences in representative CMEs and alterations in toxicity endpoints, which can potentially inform safer utilization of composite manufacturing processes.
Perineural and Systemic Dexamethasone and Ulnar Nerve Block Duration: A Randomized, Blinded, Placebo-controlled Trial in Healthy Volunteers
Authors: Maagaard Mathias , Stormholt Emma R. , Nielsen Lasse F. , Bærentzen Finn , Danker Jakob , Zachodnik Josephine , Jæger Pia , Mathiesen Ole , Andersen Jakob H.
Published: March 2023

Background

The authors hypothesized that both perineural and systemic dexamethasone as adjuncts to bupivacaine increase the duration of an ulnar nerve block compared with bupivacaine alone, and that systemic dexamethasone is noninferior to perineural dexamethasone.

Methods

The authors performed bilateral ulnar nerve blocks with 3 ml bupivacaine 5 mg/ml in 16 healthy volunteers on two trial days. According to randomization, subjects received adjunct treatment with 1 ml dexamethasone 4 mg/ml + 1 ml of saline (perineural condition) in one arm and 2 ml saline in the other arm (systemic condition, through absorption and redistribution of the contralaterally administered perineural dexamethasone) on one trial day; and 2 ml saline in one arm (placebo condition) and 2 ml of lidocaine in the other arm (lidocaine condition) on the other trial day. The primary outcome was the duration of the sensory nerve block assessed by temperature discrimination.

Results

Mean sensory block duration was 706 ± 94 min for the perineural condition, 677 ± 112 min for the systemic condition, and 640 ± 121 min for the placebo condition. The duration of the sensory nerve block was greater with perineural dexamethasone versus placebo (mean difference 66 min (95% CI, 23 to 108). Block duration was similar between systemic dexamethasone and placebo (mean difference 36 min; 95% CI, –30 to 103).

Conclusions

Perineural dexamethasone as an adjunct to bupivacaine in healthy volunteers resulted in a greater duration of an ulnar nerve block when compared with placebo. Systemic dexamethasone resulted in a similar duration as placebo.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Approach to Left Bundle Branch Pacing
Authors: Katta Maanya Rajasree , Abouzid Mohamed Riad Abdelgawad , Hameed Maha , Kaur Jasneet , Balasubramanian Suryakumar
Published: March 2023

Cardiac pacing refers to the implantation tool serving as a treatment modality for various indications, the most common of which is symptomatic bradyarrhythmia. Left bundle branch pacing has been noted in the literature to be safer than biventricular pacing or His-bundle pacing in patients with left bundle branch block (LBBB) and heart failure, thereby becoming the focus of further research on cardiac pacing. A review of the literature was conducted using a combination of keywords, including “Left Bundle Branch Block,” “Procedural techniques,” “Left Bundle Capture,” and “Complications.” The following factors have been investigated as key criteria for direct capture: paced QRS morphology, peak left ventricular activation time, left bundle potential, nonselective and selective left bundle capture, and programmed deep septal stimulation protocol. In addition, complications of LBBP, inclusive of septal perforation, thromboembolism, right bundle branch injury, septal artery injury, lead dislodgement, lead fracture, and lead extraction, have also been elaborated on. Despite clinical implications based on clinical research comparing the use of LBBP with other forms such as right ventricular apex pacing, His-bundle pacing, biventricular pacing, and left ventricular septal pacing, a paucity in the literature on long-term effects and efficacy has been noted. LBBP can thus be considered to have a promising future in patients requiring cardiac pacing, assuming that additional research on clinical outcomes and the limitation of significant complications such as thromboembolism can be established.
Surgical approach affecting long-term urinary continence status after robot-assisted laparoscopic prostatectomy prospectively evaluated using self-reported functional status (Expanded Prostate Cancer Index Composite, EPIC-26)
Authors: Reichert Mathias , Strauß Arne , Voß Joost Wilhelm , von Knobloch Hans Christoph , Neuenhofer Hannah Maria , Uhlig Annemarie , Trojan Lutz , Mohr Mirjam Naomi
Published: March 2023

Purpose

The aim of the study was to examine the influence of the surgical approach for robot-assisted laparoscopic prostatectomy (RALP) on long-term urinary continence status in the era of self-reported functional status measures using the Expanded Prostate Cancer Index Composite 26.

Materials and methods

This is a prospective evaluation of 232 patients undergoing RALP between September, 2019 and September, 2020. Urinary continence status and postoperative incontinence (pad usage) were evaluated 12 months after RALP using Expanded Prostate Cancer Index Composite 26 questionnaires. Patients were categorized according to their surgical approach and outcome into the following groups: successful nerve sparing (NS), primarily without nerve sparing (prim. NNS), and no nerve sparing by secondary resection (NNS by SR). The median levels of their questionnaire outcomes were evaluated and compared using the Wilcoxon rank sum test with continuity correction.

Results

Urinary continence status 12 months after RALP differed significantly between the NS and prim. NNS (p = 0.0071) and the NS and NNS by SR (p = 0.0076) groups. There was no significant difference between the prim. NNS and NNS by SR (p = 0.53) groups. Pad usage 12 months after RALP had no significant difference with regard to SR of the neurovascular bundle (p = 0.14).

Conclusions

Patient-reported outcomes of long-term urinary continence status seem to show no difference in postoperative continence, regardless of whether a non–nerve-sparing result was planned or reached through SR. Instead, preservation of neurovascular bundle seems to lead to better long-term continence rates.
The aging brain: risk factors and interventions for long term brain health in women
Authors: Caldwell Jessica Z.K. , Isenberg Nancy
Published: March 2023

Purpose of review

Poor cognitive aging and dementia pose a significant public health burden, and women face unique risks compared to men. Recent research highlights the role of genetics, menopause, chronic disease, and lifestyle in risk and resilience in women's cognitive aging. This work suggests avenues for clinical action at midlife that may change the course of brain health in aging.

Recent findings

Studies indicate women's risk for poor cognitive aging relates in part to hormone changes at menopause, a time when memory, brain structure and function, and Alzheimer's pathology may be observed in women and not men. Medical and lifestyle risks including diabetes, hypertension, and low physical activity also contribute to women's unique risks. At the same time, literature on resilience suggests women may benefit from lifestyle and chronic disease intervention, possibly more than men. Current studies emphasize the importance of interacting genetic and lifestyle risks, and effects of social determinants of health.

Women have greater risk than men for poor cognitive aging; however, by treating the whole person, including genetics, lifestyle, and social environment, clinicians have an opportunity to support healthy cognitive aging in women and reduce the future public health burden of dementia.
Genital tuberculosis, infertility and assisted reproduction
Authors: Mir Nousheen , Pal Lubna
Published: March 2023

Purpose of review

The goal of this review is to familiarize a global readership on the subtilities of clinical presentation and the mayhem that a missed diagnosis of genital tuberculosis (GTB) is capable of inflicting on the health and wellbeing of infertile women with untreated GTB attempting to conceive with assisted reproductive technology (ART).

Recent findings

Emerging and recent literature relating to the epidemiology and clinical presentation of GTB and reporting of unique risks of ART for maternal and fetal morbidity in untreated cases of GTB are reviewed. Evidence relating to a broadening spectrum of screening methodologies for GTB detection of GTB is additionally considered.

Genital TB must be considered as a mechanism for couple's infertility in at-risk populations. Attempting to treat female GTB-related infertility with in-vitro fertilization poses unique and potentially life-threatening risks, both to the mother and to the conceptus; these risks can be avoided through vigilance, appropriate screening and timely treatment prior to proceeding with IVF.
HENLE FIBER LAYER THICKNESS AND AREA MEASUREMENT IN TYPE 2 DIABETES MELLITUS WITH AND WITHOUT RETINOPATHY USING A MODIFIED DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY STRATEGY
Authors: Ersoz M. Giray , Kırık Furkan , Isik Burcu , Ozdemir Hakan
Published: March 2023

Purpose:

To investigate the thicknesses and areas of Henle fiber layer (HFL), outer nuclear layer, and outer plexiform layer in the eyes of patients with diabetes with no diabetic retinopathy, in eyes with nonproliferative diabetic retinopathy without diabetic macular edema, and in healthy eyes using a modified directional optical coherence tomography strategy.

Methods:

In this prospective study, the no diabetic retinopathy group included 79 participants, the nonproliferative diabetic retinopathy group comprised 68 participants, and the control group had 58 participants. Thicknesses and areas of Henle fiber layer, outer nuclear layer, and outer plexiform layer were measured on a horizontal single optical coherence tomography scan centered on the fovea using directional optical coherence tomography.

Results:

The foveal, parafoveal, and total HFL were significantly thinner in the nonproliferative diabetic retinopathy group than in the no diabetic retinopathy group and the control group (all P < 0.05). The no diabetic retinopathy group had significantly thinner foveal HFL thickness and area compared with the control group (all P < 0.05). The nonproliferative diabetic retinopathy group had significantly thicker outer nuclear layer thickness and area in all regions than the other groups (all P < 0.05). The outer plexiform layer measurements did not differ between the groups (all P > 0.05).

Conclusion:

Directional optical coherence tomography provides isolated thickness and area measurement of HFL. In patients with diabetes, the HFL is thinner, and HFL thinning begins before the presence of diabetic retinopathy.
RISK FACTORS FOR SURGERY OR BLINDNESS IN NEOVASCULAR GLAUCOMA EYES TREATED WITH ANTI-VEGF INJECTIONS BY A RETINA SPECIALIST
Authors: Massenzio Erik , Xu David , Abishek Robert , Wibbelsman Turner D. , Sheng Young , Obeid Anthony , Bhatt Shivani , Zhang Qiang , Sharpe James , Park Carl H. , Spirn Marc J. , Gupta Omesh P. , Chiang Allen , Shukla Aakriti , Shalaby Wesam S. , Myers Jonathan S. , Hsu Jason
Published: March 2023

Purpose:

To determine baseline patient characteristics that predict the need for glaucoma surgery or blindness in eyes with neovascular glaucoma (NVG) despite intravitreal antivascular endothelial growth factor therapy.

Methods:

This is a retrospective cohort study of patients with NVG who had not previously received glaucoma surgery and were treated with intravitreal antivascular endothelial growth factor injections at the time of diagnosis, from September 8, 2011, to May 8, 2020, at a large, retina subspecialty practice.

Results:

Of 301 newly presenting NVG eyes, 31% required glaucoma surgery and 20% progressed to no light perception vision despite treatment. Patients with intraocular pressure >35 mmHg (P < 0.001), two or more topical glaucoma medications (P = 0.003), worse than 20/100 vision (P = 0.024), proliferative diabetic retinopathy (P = 0.001), eye pain or discomfort (P = 0.010), and new patient status (P = 0.015) at the time of NVG diagnosis were at a higher risk of glaucoma surgery or blindness regardless of antivascular endothelial growth factor therapy. The effect of panretinal photocoagulation was not statistically significant in a subgroup analysis of patients without media opacity (P = 0.199).

Conclusion:

Several baseline characteristics at the time of presentation to a retina specialist with NVG seem to portend a higher risk of uncontrolled glaucoma despite the use of antivascular endothelial growth factor therapy. Prompt referral of these patients to a glaucoma specialist should be strongly considered.
VITREORETINAL LYMPHOMA WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT IN A PATIENT WITH SARCOIDOSIS: A CASE REPORT
Authors: Ramos Michael S. , Mammo Danny A. , Yuan Alex , Sharma Sumit
Published: March 2023

Background/Purpose:

To describe a case of primary vitreoretinal lymphoma with central nervous system involvement in a patient with sarcoidosis.

Methods:

Single, retrospective chart review.

Patient:

A 59-year-old man with sarcoidosis.

Results:

The patient presented with a 3-year history of bilateral panuveitis thought secondary to his sarcoidosis diagnosed 11 years before. Shortly before presentation, the patient demonstrated recurrent uveitis with a lack of response to aggressive immunosuppression therapy. At presentation, ocular examination showed significant anterior and posterior inflammation. Fluorescein angiography demonstrated hyperfluorescence of the optic nerve with late and small vessel leakage in the right eye. The patient also described a two-month history of memory and word-finding deficits. An inflammatory and infectious disease work-up was unremarkable. A brain MRI showed multiple enhancing periventricular lesions with vasogenic edema, whereas a lumbar puncture was negative for malignant cells. A diagnostic pars plana vitrectomy confirmed a diagnosis of large B-cell lymphoma.

Conclusion:

Sarcoidosis and vitreoretinal lymphoma are known masqueraders. Recurrent inflammation typical of sarcoid uveitis may mask a more sinister diagnosis such as vitreoretinal lymphoma. Furthermore, sarcoid uveitis treatment with corticosteroids may transiently improve symptoms, but further delay a timely diagnosis of primary vitreoretinal lymphoma.
Content Validity of a Collaborative Goal-Setting Pictorial Tool for Children Who Wear Ankle-Foot Orthoses: A Modified Delphi Consensus Study
Authors: Owen Elaine , Rahlin Mary , Kane Kyra Janine
Published: March 2023

Introduction

To determine the optimum prescription and dosage for an ankle-foot orthosis and footwear, clinicians and families need to agree on goals for intervention. To facilitate family-centered collaborative goal setting, a table of potential goals and its pictorial representation had been developed previously. These tools incorporated the International Classification of Functioning, Disability, and Health (ICF) and International Organization for Standardization (ISO) clinical objectives for orthoses and were structured in an approach understandable to families. This study aimed to obtain consensus on the content validity of the Table and Pictorial Tools.

Methods

Seventeen experts from seven countries (orthotists, physical therapists, physicians, surgeons, and engineers) were invited. A modified Delphi technique was used to evaluate and refine the Table Tool (rounds 1 and 2) and Pictorial Tool (rounds 3 and 4). Participants rated their agreement with overall tool structure, content, and feasibility of use on a 4-point Likert scale, and provided open-ended feedback. Consensus was defined as a median score ≥3 (agree) with 75% of responses ≥3. Data were collected using REDCap. After each round, thematic analysis guided document revisions and anonymized feedback.

Results

Ten experts from four countries completed the study. Round 1 (Table Tool): median ratings were all 3; consensus was achieved for 3/5 questions. Round 2: full consensus was achieved. Round 3 (Pictorial Tool): median ratings were ≥3 for 10/11 questions; consensus was achieved for 4/11 questions. Round 4: full consensus was achieved.

Conclusions

The content validity for the Table and Pictorial Tools was established by modified Delphi consensus. These tools represent a comprehensive selection of goals across all ICF components.

Clinical Relevance

These novel tools have the potential to facilitate collaborative goal setting between families and clinicians and aid clinical education. A goal-setting framework specific to orthotic management may improve outcomes within the context of family-centered care.
Clinical outcomes and quality of life after contemporary isolated coronary bypass grafting: a prospective cohort study
Authors: Sandner Sigrid , Misfeld Martin , Caliskan Etem , Böning Andreas , Aramendi Jose , Salzberg Sacha P. , Choi Yeong-Hoon , Perrault Louis P. , Tekin Ilker , Cuerpo Gregorio P. , Lopez-Menendez Jose , Weltert Luca P. , Böhm Johannes , Krane Markus , González-Santos José M. , Tellez Juan-Carlos , Holubec Tomas , Ferrari Enrico , Doros Gheorghe , Vitarello Clara J. , Emmert Maximilian Y. ,   on behalf of the Registry Investigators; European DuraGraft Registry investigators’
Published: March 2023

Objectives:

The objective of the European Multicenter Registry to Assess Outcomes in coronary artery bypass grafting (CABG) patients (DuraGraft Registry) was to determine clinical outcomes and quality of life (QoL) after contemporary CABG that included isolated CABG and combined CABG/valve procedures, using an endothelial damage inhibitor (DuraGraft) intraoperatively for conduit preservation. Here, we report outcomes in the patient cohort undergoing isolated CABG.

Methods:

The primary outcome was the composite of all-cause death, myocardial infarction (MI), or repeat revascularization (RR) [major adverse cardiac events (MACE)] at 1 year. Secondary outcomes included the composite of all-cause death, MI, RR, or stroke [major adverse cardiac and cerebrovascular events (MACCE)], and QoL. QoL was assessed with the EuroQol-5 Dimension questionnaire. Independent risk factors for MACE at 1 year were determined using Cox regression analysis.

Results:

A total of 2532 patients (mean age, 67.4±9.2 years; 82.5% male) underwent isolated CABG. The median EuroScore II was 1.4 [interquartile range (IQR), 0.9–2.3]. MACE and MACCE rates at 1 year were 6.6% and 7.8%, respectively. The rates of all-cause death, MI, RR, and stroke were 4.4, 2.0, 2.2, and 1.9%, respectively. The 30-day mortality rate was 2.3%. Age, extracardiac arteriopathy, left ventricular ejection fraction less than 50%, critical operative state, and left main disease were independent risk factors for MACE. QoL index values improved from 0.84 [IQR, 0.72–0.92] at baseline to 0.92 [IQR, 0.82–1.00] at 1 year (P<0.0001).

Conclusion:

Contemporary European patients undergoing isolated CABG have a low 1-year clinical event rate and an improved QoL.
Can prophylactic tamsulosin reduce the risk of urinary retention after surgery? A systematic review and meta-analysis of randomized control trials
Authors: Zhou Zhaohui , Gan Wenyi , Li Zhiyong , Li Zhen , Zhou Fangjian , Li Hua , Liu Zhuowei
Published: March 2023

Objective:

The meta-analysis aimed to integrate the evidence of randomized control trials to estimate the efficacy of prophylactic tamsulosin on postoperative urinary retention (POUR).

Methods:

The PubMed, Embase, Web of Science, and Cochrane Library databases were searched through 1 March 2022 using predetermined keywords. Randomized control trials reporting the preventive efficacy of prophylactic tamsulosin against POUR were identified according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guideline. Pooled risk ratios (RRs) were calculated using a random-effects model or a fixed-effects model based on the results of heterogeneity assessment. A meta-regression analysis was performed to explore the potential sources of heterogeneity.

Results:

There were 14 studies with 1102 patients in the Tamsulosin group and 1119 patients in the Control group. The risk of POUR was significantly lower in the Tamsulosin group (156/1102 [14.2%] vs. 238/1119 [21.3%]; RR=0.65; 95% CI: 0.50–0.86; P=0.002; Heterogeneity: I
2=51%; P=0.01). Tamsulosin administration was associated with a higher risk of adverse events (65/614 [10.6%] vs. 39/626 [6.2%]; RR=1.72; 95% CI: 1.19–2.48; P=0.004; Heterogeneity: I
2=0%; P=0.70). The meta-regression identified the mean age of patients as the only potential source of heterogeneity. Subgroup analysis showed that the younger patients (age <50 years) might benefit more from tamsulosin intake (RR=0.36; 95% CI: 0.19–0.70; P=0.003; Heterogeneity: I
2=49%; P=0.14).

Conclusions:

The current meta-analysis suggested that prophylactic tamsulosin contributed to the prevention of POUR, and younger patients (<50 years) might benefit more from this preventive regimen. Tamsulosin was also associated with a higher risk of adverse events.
Collecting Knowledge about Medicinal Ingredients in Northwestern Sichuan in the 1950s
Authors: Wuyutong YAO
Published: March 2023

This article explores China’s state-level knowledge production on medicinal ingredients in northwestern Sichuan in the 1950s. Drawing on county-level archives, published materials and interviews, this historical article traces how different levels of governments and state-owned trading companies produced knowledge about medicinal ingredients and its production. It argues that on one hand the state’s procurement standards codified the knowledge about medicinal ingredients from the marketplace and the local producers. On the other hand, direct extraction of knowledge from the medicine gatherers and cultivators verbalized and collected the previously tacit local knowledge about the production of medicinal ingredients, which would help to alleviate the shortage in the supply of traditional Chinese medicines throughout the 1950s.
Uromodulin: more than a marker for chronic kidney disease progression
Authors: LaFavers Kaice , Garimella Pranav S.
Published: March 2023

Purpose of review

Uromodulin, a protein that is highly conserved across several species through evolution, functions to maintain homeostasis and prevent disease development and progression. Historically, the role of uromodulin has been thought to be limited to the kidney and genitourinary tract. This review highlights developments indicating a broader role of uromodulin in human health.

Recent findings

Although initially discovered in the urine and found to have immunomodulatory properties, recent findings indicate that serum uromodulin (sUMOD) is distinct from urine uromodulin (uUMOD) in its structure, function, and regulation. uUMOD binds pathogenic bacteria in the urine preventing infection and is also upregulated in kidneys undergoing repair after injury. Uromodulin knockout mice exhibit higher mortality in the setting of sepsis which is also associated with upregulation of sUMOD. sUMOD lowers calcification risk but this may be influenced by presence of kidney disease.

Uromodulin is an evolutionarily conserved protein produced exclusively in the kidney tubule cells with evolving roles being reported both in the kidney and systemically. Further research should be focused at harnessing its use as a potential therapeutic.
Beyond donation to organ utilization in the USA
Authors: Stewart Darren , Hasz Richard , Lonze Bonnie
Published: March 2023

Purpose of review

The deceased donor organ pool has broadened beyond young, otherwise healthy head trauma victims. But an abundance of donated organs only benefits patients if they are accepted, expeditiously transported and actually transplanted. This review focuses on postdonation challenges and opportunities to increase the number of transplants through improved organ utilization.

Recent findings

We build upon recently proposed changes in terminology for measuring organ utilization. Among organs recovered for transplant, the nonuse rate (NURREC) has risen above 25% for kidneys and pancreata. Among donors, the nonuse rate (NURDON) has risen to 40% for livers and exceeds 70% for thoracic organs. Programme-level variation in offer acceptance rates vastly exceeds variation in the traditional, 1-year survival benchmark. Key opportunities to boost utilization include donation after circulatory death and hepatitis C virus (HCV)+ organs; acute kidney injury and suboptimal biopsy kidneys; older and steatotic livers.

Underutilization of less-than-ideal, yet transplant-worthy organs remains an obstacle to maximizing the impact of the U.S. transplant system. The increased risk of inferior posttransplant outcomes must always be weighed against the risks of remaining on the waitlist. Advanced perfusion technologies; tuning allocation systems for placement efficiency; and data-driven clinical decision support have the potential to increase utilization of medically complex organs.
The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans
Authors: Toikumo Sylvanus , Vickers-Smith Rachel , Jinwala Zeal , Xu Heng , Saini Divya , Hartwell Emily , Venegas Mirko P. , Sullivan Kyle A. , Xu Ke , Jacobson Daniel A. , Gelernter Joel , Rentsch Christopher T. ,   Million Veteran Program, Stahl Eli , Cheatle Martin , Zhou Hang , Waxman Stephen G. , Justice Amy C. , Kember Rachel L. , Kranzler Henry R.
Published: March 2023

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids played a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 125 independent genetic loci, 82 of which are novel. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level, and cognitive traits. Integration of the GWAS findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, beta-blockers, and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.
scBubbletree: quantitative visualization of single cell RNA-seq data
Authors: Kitanovski Simo , Cao Yingying , Ttoouli Dimitris , Farahpour Farnoush , Wang Jun , Hoffmann Daniel
Published: March 2023

Motivation: Visualization approaches transform high-dimensional data from single cell RNA sequencing (scRNA-seq) experiments into two-dimensional plots that are used for analysis of cell relationships, and as a means of reporting biological insights. Yet, many standard approaches generate visuals that suffer from overplotting, lack of quantitative information, and distort global and local properties of biological patterns relative to the original high-dimensional space. Results: We present scBubbletree, a new, scalable method for visualization of scRNA-seq data. The method identifies clusters of cells of similar transcriptomes and visualizes such clusters as "bubbles" at the tips of dendrograms (bubble trees), corresponding to quantitative summaries of cluster properties and relationships. scBubbletree stacks bubble trees with further cluster-associated information in a visually easily accessible way, thus facilitating quantitative assessment and biological interpretation of scRNA-seq data. Availability and Implementation: the R package scBubbletree is freely available at: https://bioconductor.org/packages/scBubbletree/ Contact: simo.kitanovski@uni-due.de, daniel.hoffmann@uni-due.de
Molecular diversity of bivalve transmissible neoplasia of blue mussels in the Kola Bay (Barents Sea) indicates a recent migration of the cancer lineages between the North Pacific and Northern Europe
Authors: Skazina M. , Ponomartsev N. , Maiorova M. , Dolganova I. , Khaitov V. , Marchenko J. , Lentsman N. , Odintsova N. , Strelkov P.
Published: March 2023

Bivalve transmissible neoplasia (BTN) is a leukemia-like cancer “metastasizing” by transmission of living cancer cells between molluscs. Blue mussels harbor two evolutionary lineages of BTN,MtrBTN1 andMtrBTN2, both derived fromMytilus trossulus. WhileMtrBTN1 has been found only inM. trossulusin North Pacific,MtrBTN2 parasitizes differentMytilusspecies worldwide, particularly in Western Europe. No targeted studies of BTN in Northern European mussels (M. edulis,M. trossulus) have been made. We searched for BTN in mussels from the Kola Bay (Barents Sea) with the help of flow cytometry of the hemolymph, qPCR with primers specific to cancer-associated alleles and sequencing of mitochondrial and nuclear loci. The species of the mussel hosts was ascertained genetically. BothMtrBTN1 andMtrBTN2 were present in our material, though their prevalence was low (∼0.4%). The only instance ofMtrBTN2 was found inM. trossulus.MtrBTN1 occurred inM. trossulusand in a hybrid betweenM. trossulusandM. edulis. This finding indicates thatMtrBTN1 may potentially infect the latter species. The mtDNA haplotypes found in both lineages were nearly identical to those known from the North Pacific, but not from elsewhere. Our results suggest that they arrived in the Kola Bay fairly recently, probably with the maritime transport along the Northern Sea Route, and that the invasion was independent of that in Western Europe. A relatively young evolutionary age ofMtrBTN1 seems to suggest that it is an emerging disease in the process of niche expansion.
Nondestructive Spatial Lipidomics for Glioma Classification
Authors: Martella Davide Alessandro , Rose Leor Ariel , Rouatbi Nadia , Gu Chenlei , Caprettini Valeria , Jensen Magnus , Hagemann Cathleen , Serio Andrea , Al-Jamal Khuloud , Parsons Maddy , Bergholt Mads , Brennan Paul , Zaritsky Assaf , Chiappini Ciro
Published: March 2023

Mapping the molecular composition of tissues using spatial biology provides high-content information for molecular diagnostics. However, spatial biology approaches require invasive procedures to collect samples and destroy the investigated tissue, limiting the extent of analysis, particularly for highly functional tissues such as those of the brain. To address these limitations, we developed a workflow to harvest biomolecules from brain tissues using nanoneedles and characterise the distribution of lipids using desorption electrospray ionization mass spectrometry imaging. The nanoneedles preserved the original tissue while harvesting a reliable molecular profile and retaining the original lipid distribution for mouse and human brain samples, accurately outlining the morphology of key regions within the brain and tumour lesions. The deep neural network analysis of a cohort containing 23 human glioma biopsies showed that nanoneedle samples maintain the molecular signatures required to accurately classify disease state. Thus, nanoneedles provide a route for tissue-preserving spatial lipidomic and molecular diagnostics.
The GlycoPaSER prototype as a real-time N-glycopeptide identification tool based on the PaSER parallel computing platform
Authors: Armony Gad , Brehmer Sven , Srikumar Tharan , Pfennig Lennard , Zijlstra Fokje , Trede Dennis , Kruppa Gary , Lefeber Dirk J. , van Gool Alain J. , Wessels Hans J.C.T.
Published: March 2023

Real-time database searching allows for simpler and automated proteomics workflows as it eliminates technical bottlenecks in high throughput experiments. Most importantly, it enables results dependent acquisition (RDA) where search results can be used to guide data acquisition during acquisition. This is especially beneficial for glycoproteomics since the wide range of physicochemical properties of glycopeptides lead to a wide range of optimal acquisition parameters. We established here the GlycoPaSER prototype by extending the Parallel Search Engine in Real-time (PaSER) functionality for real-time glycopeptide identification from fragmentation spectra. Glycopeptide fragmentation spectra were decomposed into peptide- and glycan-moiety spectra using common N-glycan fragments. Each moiety was subsequently identified by a specialized algorithm running in real-time. GlycoPaSER can keep up with the rate of data acquisition for real-time analysis with similar performance to other glycoproteomics software and produces results that are in line with literature reference data. The GlycoPaSER prototype presented here provides the first proof-of-concept for real-time glycopeptide identification that unlocks future development of RDA technology to transcend data acquisition.
A rapid, multiplex digital PCR assay forEGFR,KRAS,BRAF,ERBB2variants andALK,RET,ROS1,NTRK1gene fusions in non-small cell lung cancer
Authors: Leatham Bryan , McNall Katie , Subramanian Hari K. , Jacky Lucien , Alvarado John , Yurk Dominic , Wang Mimi , Green Donald C. , Tsongalis Gregory J. , Rajagopal Aditya , Schwartz Jerrod J.
Published: March 2023

Digital PCR (dPCR) is emerging as an ideal platform for the detection and tracking of genomic variants in cancer due to its high sensitivity and simple workflow. The growing number of clinically-actionable cancer biomarkers creates a need for fast, accessible methods that allow for dense information content and high accuracy. Here, we describe a proof-of-concept amplitude modulation based multiplex dPCR assay capable of detecting 12 single nucleotide and indel variants inEGFR,KRAS,BRAF, andERBB2,14 gene fusions inALK, RET, ROS1, NTRK1,andMETexon 14 skipping present in non-small cell lung cancer (NSCLC). We also demonstrate the use of multi-spectral target signal encoding to improve the specificity of variant detection by reducing background noise up to 11-fold. The assay reported an overall 100% PPA and 98.5% NPA compared to a sequencing-based assay in a cohort of 62 human FFPE samples. In addition, the dPCR assay rescued actionable information in 10 samples that failed to sequence, highlighting the utility of a multiplexed digital assay as a potential reflex solution for challenging NSCLC samples.
Multidimensional proteomics identifies molecular trajectories of cellular aging and rejuvenation
Authors: Leutert Mario , Armstrong Joe , Ollodart Anja R. , Hess Kyle , Muir Michael , Rodriguez-Mias Ricard A. , Kaeberlein Matt , Dunham Maitreya , Villén Judit
Published: March 2023

The declining capacity of cells to maintain a functional proteome is a major driver of cellular dysfunction and decreased fitness in aging. Here we assess the impact of aging on multiple proteome dimensions, which are reflective of function, across the replicative lifespan ofSaccharomyces cerevisiae. We quantified protein abundance, protein turnover, protein thermal stability, and protein phosphorylation in mother yeast cells and their derived progeny at different ages. We find progressive and cumulative proteomic alterations that are reflective of dysregulation of complex assemblies, mitochondrial remodeling, post-translational activation of the AMPK/Snf1 energy sensor in mother cells, and an overall shift from biosynthetic to energy-metabolic processes. Our multidimensional proteomic study systematically corroborates previous findings of asymmetric segregation and daughter cell rejuvenation, and extends these concepts to protein complexes, protein phosphorylation, and activation of signaling pathways. Lastly, profiling age-dependent proteome changes in a caloric restriction model of yeast provided mechanistic insights into longevity, revealing minimal remodeling of energy-metabolic pathways, improved mitochondrial maintenance, ameliorated protein biogenesis, and decreased stress responses. Taken together, our study provides thousands of age-dependent molecular events that can be used to gain a holistic understanding of mechanisms of aging.
Hiding in Plain Sight: Phylogenomics Reveals a New Branch on the Noctuoidea Tree of Life
Authors: St Laurent Ryan A. , Goldstein Paul Z. , Miller Scott E. , Robbins Robert K.
Published: March 2023

We present the results of the first phylogenomic analyses based on anchored hybrid enrichment (AHE) data from densely sampled tribes and subfamilies of Notodontidae (Prominent Moths). Our analyses reveal the family’s polyphyly with respect to an assemblage of genera related toScranciaHolland that has been variously recognized at the tribal or subfamilial rank. We propose and re-describe Scranciidae,stat. nov., and recognize 21 genera and approximately 100 species—distributed in Africa, Asia, and Australia and not represented in previous phylogenomic studies—from the six recognized noctuoid families (Noctuidae, Erebidae, Euteliidae, Nolidae, Notodontidae, and Oenosandridae). We further re-interpret morphological synapomorphies previously proposed for Notodontidae (including Scranciidae) and for the trifid Noctuoidea,viz.the ventral-facing tympanum and trifid forewing venation— characters previously called into question when Doidae were transferred from Noctuoidea to Drepanoidea. Deep-level relationships within Noctuoidea are not firmly established outside the clade comprising the four quadrifid families (Noctuidae, Erebidae, Euteliidae, and Nolidae), and in attempting to establish the phylogenetic position of Scranciidae relative to Notodontidae, Oenosandridae, and the quadrifids, we obtain conflicting results depending on data type (amino acid vs. nucleotide) and analytical framework (maximum likelihood, multi-species coalescent, and parsimony). We also demonstrate that discordant topologies among these ancient lineages yield drastically different divergence time estimates, highlighting the need for caution when interpreting phylogenetic dating of uncertain topologies. Following multiple analyses of several datasets designed around the distribution of missing data, and an evaluation of strict support measures at the deepest nodes of the noctuoid tree, we provisionally conclude that this ambiguity is a function of character conflict amplified by missing data and short branch lengths, and that in the topology best supported by the available data, Scranciidae is placed well outside Notodontidae and sister to the remaining Noctuoidea.
Pathology of natural infection with highly pathogenic avian influenza virus (H5N1) clade 2.3.4.4b in wild terrestrial mammals in the United States in 2022
Authors: Elsmo EJ , Wünschmann A , Beckmen KB , Broughton-Neiswanger LB , Buckles EL , Ellis J , Fitzgerald SD , Gerlach R , Hawkins S , Ip HS , Lankton JS , Lemley EM , Lenoch JB , Killian ML , Lantz K , Long L , Maes R , Mainenti M , Melotti J , Moriarty ME , Nakagun S , Ruden RM , Shearn-Bochsler V , Thompson D , Torchetti MK , Van Wettere AJ , Wise AG , Lim AL
Published: March 2023

This article describes the first detections of disease due to natural infection with highly pathogenic avian influenza virus (HPAIv) H5N1 of the Eurasian lineage goose/Guangdong clade 2.3.4.4b in wild terrestrial mammals throughout the United States during 2021-2022. Affected mammalian species include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). Infected mammals primarily exhibited neurological signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.
Impact of Socioeconomic Status on Amygdala and Hippocampus Subdivisions in Children and Adolescents
Authors: Hanson Jamie L , Adkins Dorthea J , Nacewicz Brendon M , Barry Kelly R
Published: March 2023

Socioeconomic status (SES) in childhood can impact behavioral and brain development. Past work has consistently focused on the amygdala and hippocampus, two brain areas critical for emotion and behavioral responding. While there are SES differences in amygdala and hippocampal volumes, there are many unanswered questions in this domain connected to neurobiological specificity, and for whom these effects may be more pronounced. We may be able to investigate some anatomical subdivisions of these brain areas, as well as if relations with SES vary by participant age and sex. No work to date has however completed these types of analyses. To overcome these limitations, here, we combined multiple, large neuroimaging datasets of children and adolescents with information about neurobiology and SES (N=2,765). We examined subdivisions of the amygdala and hippocampus and found multiple amygdala subdivisions, as well as the head of the hippocampus, were related to SES. Greater volumes in these areas were seen for higher-SES youth participants. Looking at age- and sex-specific subgroups, we tended to see stronger effects in older participants, for both boys and girls. Paralleling effects for the full sample, we see significant positive associations between SES and volumes for the accessory basal amygdala and head of the hippocampus. We more consistently found associations between SES and volumes of the hippocampus and amygdala in boys (compared to girls). We discuss these results in relation to conceptions of “sex-as-a-biological variable” and broad patterns of neurodevelopment across childhood and adolescence. These results fill in important gaps on the impact of SES on neurobiology critical for emotion, memory, and learning.