bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro
and
in vivo
activities of KSP-1007, a broad-spectrum inhibitor of serine- and metallo-β-lactamases, in combination with meropenem against carbapenem-resistant Gram-negative bacteria
Authors: Takemoto Koji , Nakayama Ryo , Fujimoto Koichi , Suzuki Yumiko , Takarabe Yukiko , Honsho Masako , Kitahara Sachiko , Noguchi Yoshihiko , Matsui Hidehito , Hirose Tomoyasu , Asami Yukihiro , Hidaka Jun , Sunazuka Toshiaki , Hanaki Hideaki
Published: May 2024

KSP-1007 is a novel bicyclic boronate-based broad-spectrum β-lactamase inhibitor and is being developed in combination with meropenem (MEM) for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria, a global health concern, and here, we describe its characteristics. KSP-1007 exhibited low apparent inhibition constant (

K
i

app
) values against all classes of β-lactamase, including imipenemase types and oxacillinase types from
Acinetobacter baumannii
. Against 207
Enterobacterales
and 55
A
.
baumannii
, including carbapenemase producers, KSP-1007 at fixed concentrations of 4, 8, and 16 µg/mL dose-dependently potentiated the
in vitro
activity of MEM in broth microdilution MIC testing. The MIC
90
of MEM/KSP-1007 at 8 µg/mL against
Enterobacterales
was lower than those of MEM/vaborbactam, ceftazidime/avibactam, imipenem/relebactam, and colistin and similar to those of aztreonam/avibactam, cefiderocol, and tigecycline. The
in vitro
activity of MEM/KSP-1007 at ≥4 µg/mL against
Enterobacterales
harboring metallo-β-lactamase was superior to that of cefepime/taniborbactam. MEM/KSP-1007 showed excellent activity against
Escherichia coli
with PBP3 mutations and New Delhi metallo-β-lactamase compared to aztreonam/avibactam, cefepime/taniborbactam, and cefiderocol. MEM/KSP-1007 at 8 µg/mL showed greater efficacy against
A. baumannii
than these comparators except for cefiderocol, tigecycline, and colistin. A 2-fold reduction in MEM MIC against 96
Pseudomonas aeruginosa
was observed in combination with KSP-1007. MEM/KSP-1007 demonstrated bactericidal activity against carbapenemase-producing
Enterobacterales
,
A. baumannii
, and
P. aeruginosa
based on minimum bactericidal concentration/MIC ratios of ≤4. KSP-1007 enhanced the
in vivo
activity of MEM against carbapenemase-producing
Enterobacterales
,
A. baumannii
, and
P. aeruginosa
in murine systemic, complicated urinary tract, and thigh infection models. Collectively, MEM/KSP-1007 has a good profile for treating carbapenem-resistant Gram-negative bacterial infections.
Multiple E3 ligases act as antiviral factors against SARS-CoV-2 via inducing the ubiquitination and degradation of ORF9b
Authors: Yu Miao , Li Jie , Gao Wenying , Li Zhaolong , Zhang Wenyan
Published: May 2024

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) open reading frame 9b (ORF9b) antagonizes the antiviral type I and III interferon (IFN) responses and is ubiquitinated and degraded via the ubiquitin-proteasome pathway. However, E3 ubiquitin ligases that mediate the polyubiquitination and degradation of ORF9b remain unknown. In this study, we identified 14 E3 ligases that specifically bind to SARS-CoV-2 ORF9b. Specifically, three E3 ligases, HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 (HUWE1), ubiquitin protein ligase E3 component n-recognin 4 (UBR4), and UBR5, induced K48-linked polyubiquitination and degradation of ORF9b, thereby attenuating ORF9b-mediated inhibition of the IFN response and SARS-CoV-2 replication. Moreover, each E3 ligase performed this function independent of the other two E3 ligases. Therefore, the three E3 ligases identified in this study as anti-SARS-CoV-2 host factors provide novel molecular insight into the virus-host interaction.

IMPORTANCE

Ubiquitination is an important post-translational modification that regulates multiple biological processes, including viral replication. Identification of E3 ubiquitin ligases that target viral proteins for degradation can provide novel targets for antagonizing viral infections. Here, we identified multiple E3 ligases, including HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 (HUWE1), ubiquitin protein ligase E3 component n-recognin 4 (UBR4), and UBR5, that ubiquitinated and induced the degradation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) open reading frame 9b (ORF9b), an interferon (IFN) antagonist, thereby enhancing IFN production and attenuating SARS-CoV-2 replication. Our study provides new possibilities for drug development targeting the interaction between E3 ligases and ORF9b.
Microbroth dilution method for antibiotic susceptibility testing of fastidious and anaerobic bacteria of the urinary microbiome
Authors: Geaman Wilson , Choi Brian I. , Kaindl Jacob , Gonzalez Caroline , Wolfe Alan J.
Published: May 2024

Bacterial isolates from the human urinary microbiome have been extensively studied for their antibiotic resistance; however, little work has been done on those isolates that are difficult to grow
in vitro
. This study was designed to qualify a serum-based medium, New York City Broth III (NYCIII), and a broth microdilution method to determine the antibiotic susceptibility of previously underreported or undescribed microbes that have a difficult time growing in standard Mueller-Hinton broth. Here, we demonstrate that NYCIII microbroth dilution can be an effective method for the determination of antibiotic susceptibility of species found in the human urinary microbiome. We show that this method serves well to characterize fastidious and anaerobic urinary microbes that have no Clinical and Laboratory Standards Institute (CLSI) guidelines, including several in the families
Aerococcaceae
,
Lactobacillaceae
, or
Actinomycetaceae
. Previous studies using expanded quantitative urine culture reveal that urine samples from clinical patients are commonly polymicrobial in composition. Thus, we test whether NYCIII can serve as a viable harmonized medium, capable of supporting antibiotic susceptibility testing in a range of fastidious, non-fastidious, and anaerobic urinary microbes. We propose this methodology to be standardized comparable to CLSI standards to allow for resistance testing in uncharacterized urinary bacteria.

IMPORTANCE

Antibiotic susceptibilities of fastidious and anaerobic bacteria of the human urinary microbiome are largely underreported due to difficulty in growing them in the lab environment. The current standard medium, Muller-Hinton broth, has difficulty supporting the growth of many of these species, leaving microbiologists without a standardized method. To address this need, this study offers a methodology to survey susceptibilities in a high-throughput manner of these understudied microbes with a proposed harmonized medium, NYCIII, which is capable of supporting the growth of both fastidious and non-fastidious urinary microbes. Broader standardization of this method can allow for the development of antibiotic-resistant breakpoints of the many uncharacterized urinary microbes.
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

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

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

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.
Supplemental Material: Millennial-scale climate cycles modulated by Milankovitch forcing in the middle Cambrian (ca. 500 Ma) Marjum Formation, Utah, USA
Authors: Pas Damien , al. et
Published: May 2024

Methods, depositional model, Figures S1–S6, and time series analysis scripts, and data.  
Secondary bacterial corneal infection caused byMyroidesspecies in primary fungal keratitis
Authors: Malepati Nikhila , Mitra Sanchita , Chandran Kavya , Shanbhag Swapna S
Published: May 2024

A middle-aged male patient presented with a central corneal perforation in a deep stromal infiltrate in his left eye. An emergency therapeutic penetrating keratoplasty was performed. Microbiological evaluation of the corneal scraping specimen revealed septate fungal filaments on stains. However, culture reports after 24 hours from the scraping sample and the excised half corneal button showed growth of gram-negative bacilli. This pathogen was identified as an aerobic, non-fermentative, gram-negative, bacillus by conventional microbiology and confirmed asMyroidesspecies by the VITEK 2 Compact system (bioMérieux, Marcy l’Etoile, France). Susceptibility to chloramphenicol was noted based on which the patient was treated with topical chloramphenicol 0.5%. No recurrence of the infection was noted. This is the first reported case of corneal infection with theMyroidesspecies of bacteria which, heretofore, have been known to cause endocarditis and urinary tract infections.
Brexpiprazole toxicity in a paediatric patient
Authors: Akel Mohamad Bisher , Condren Michelle E , Passmore Sarah J
Published: May 2024

Brexpiprazole is a relatively new drug that has no published research or applications within the paediatric population. Brexpiprazole targets multiple receptors and can manifest as multisystem symptoms when ingested in supratherapeutic quantities. In this report, we discuss the case of a child in early childhood who presented with delayed neurological and cardiac symptoms 24 hours after accidental ingestion of brexpiprazole. Due to delayed onset, this case highlights that a high index of suspicion and prolonged observation are necessary to appropriately manage brexpiprazole overdose or accidental ingestion.
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

Purpose

To 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.

Methods

Prospective 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).

Results

Standardised 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).

Conclusions

DR-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

Introduction

Recent 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.

Methods

We 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.

Results

Empirical 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.

Conclusions

Niger 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

Background

Exploring 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.

Methods

A 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.

Results

The 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.

Conclusion

This 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.
Comprehensive imaging analysis of intracranial atherosclerosis
Authors: Sanchez Sebastian , Mossa-Basha Mahmud , Anagnostakou Vania , Liebeskind David S , Samaniego Edgar A
Published: May 2024

Intracranial atherosclerotic disease (ICAD) involves the build-up of atherosclerotic plaques in cerebral arteries, significantly contributing to stroke worldwide. Diagnosing ICAD entails various techniques that measure arterial stenosis severity. Digital subtraction angiography, CT angiography, and magnetic resonance angiography are established methods for assessing stenosis. High-resolution MRI offers additional insights into plaque morphology including plaque burden, hemorrhage, remodeling, and contrast enhancement. These metrics and plaque traits help identify symptomatic plaques. Techniques like transcranial Doppler, CT perfusion, computational fluid dynamics, and quantitative MRA analyze blood flow restrictions due to ICAD. Intravascular ultrasound or optical coherence tomography have a very high spatial resolution and can assess the structure of the arterial wall and the plaque from the lumen of the target vascular territory. Positron emission tomography could further detect inflammation markers. This review aims to provide a comprehensive overview of the spectrum of current modalities for atherosclerotic plaque analysis and risk stratification.
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

Introduction

Transition-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.

Methods

We 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.

Results

Of 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.

Discussion

Despite 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.
Remote sensing of biogeophysical variables at the Cape Bounty Arctic Watershed Observatory, Melville Island, Nunavut, Canada
Authors: Treitz P.M. , Atkinson D.M. , Blaser A. , Bonney M.T. , Braybrook C.A. , Buckley E.C. , Collingwood A. , Edwards R. , van Ewijk K. , Freemantle V. , Gregory F. , Holloway J. , Hung J.K.Y. , Lamoureux S.F. , Liu N. , Ljubicic G. , Robson G. , Rudy A.C.A. , Scott N.A. , Shang C. , Wall J.
Published: May 2024

The Cape Bounty Arctic Watershed Observatory (CBAWO), Melville Island, Nunavut (74°55′N, 109°34′W) was established in 2003 to examine Arctic ecosystem processes that would be impacted by climate warming and permafrost degradation. This paper provides a synthesis of how remote sensing has contributed to biogeophysical modelling and monitoring at the CBAWO from 2003 to 2023. Given the location and isolated nature of the CBAWO in the Canadian High Arctic, remote sensing data and derivatives have been instrumental for studies examining ecosystem structure and function at local and landscape scales. In combination with field measurements, remote sensing data facilitated mapping and modelling of vegetation types, % vegetation cover and aboveground phytomass, soil moisture, carbon exchange rates, and permafrost degradation and disturbance. It has been demonstrated that even in an environment with limited vegetation cover and phytomass, spectral vegetation indices (e.g., the normalized difference vegetation index) are able to model various biogeophysical variables. These applications are feasible for research sites such as the CBAWO using high spatial resolution remote sensing data across the visible, infrared, and microwave regions of the electromagnetic spectrum. Furthermore, as the satellite record continues to expand, we will gain a greater understanding of the impacts arising from the expected continued warming at northern latitudes. Although the logistics for research in the Arctic remain challenging, today's technologies (e.g., high spatial resolution satellite remote sensing, automated in situ sensors and data loggers, and wireless communication systems) can support a host of scientific endeavours in the Arctic (and other remote sites) through modelling and monitoring of biogeophysical variables and Earth surface processes with limited but critical field campaigns. The research synthesized here for the CBAWO highlights the essential role of remote sensing of terrestrial ecosystems in the Canadian Arctic.
The pattern of reproduction in the African giant pouched rat, Cricetomys gambianus, from Tanzania: unravelling the environmental triggers for breeding
Authors: Ngalameno M.K. , Luziga C. , Hart D.W. , Bennett N.C.
Published: May 2024

Our research represents the first extensive study of the breeding behaviour and related environmental triggers of reproduction in the African giant pouch rat ( Cricetomys gambianus Waterhouse, 1840) in and around the equator throughout a whole year. We measured the gross morphology and detailed histology of both female and male rats, along with plasma steroid hormone levels. Contrary to other tropical-dwelling small mammals, the African giant pouch rat is a seasonal breeder; however, rainfall is not to be the primary cue of reproduction. Our study suggests that ambient temperature and photoperiod are the primary environmental cues of reproduction, with breeding occurring during the cooler months of the year, namely in the dry season. During the wet and hot season, which succeeds the dry season, there is an increase in the availability of quality food, which results in nursing mothers and weaned pups achieving a positive energy balance and increased body condition. This, in turn, increases pregnancy success and offspring survival. Climate change, particularly global warming, could harm the reproduction of African giant pouched rats as rising temperatures in and around the equator, including Tanzania, may impact their circannual reproductive cycle.
Gastropod shell differentiation following colonization of an invasive intertidal macrophyte in Atlantic Canada
Authors: Reimchen T.E. , Holden J. , Cortese A.R.B.
Published: May 2024

In the 19th century, a lower intertidal macrophyte, Fucus serratus (Linnaeus) , from western Europe was introduced to Nova Scotia, Canada, where it successfully established, co-existing with native macrophytes Fucus vesiculosus (Linnaeus) and Ascophyllum nodosum (Linnaeus). We first examined whether a common gastropod in Nova Scotia, Littorina obtusata (Linnaeus, 1758), which grazes on the native macrophytes, has exploited the invasive and on finding this, we secondly examined whether there has been any phenotypic differentiation on the invasive. Among 98 sites surveyed around Nova Scotia and Newfoundland in May and June 1994, 11 had the invasive macrophyte, all of which showed colonization by L. obtusata including egg masses, juveniles, and adults . Among 2135 shells photographed for digital image analyses, those on the invasive differed from those on the native macrophytes with respect to (1) RGB (red/green/blue) channels, (2) HSV (hue, saturation, brightness) phenotypes, (3) protoconch pattern, and (4) adult shell size. Nitrogen and carbon stable isotope signatures on muscle tissues from a subset of L. obtusata indicate foraging fidelity on the invasive rather than temporary occupation. We suggest that these cumulative phenotypic responses to the invasive macrophyte that vary in extent and direction within and among localities reflect localized adaptation and offer a unique opportunity for quantifying early stages of phenotypic and genomic differentiation in a novel ecological niche.
Health Capacity to Work among Older Persons in Asia: Key Findings from a Regional Comparative Study
Authors: KIKKAWA AIKO , OSHIO TAKASHI , SAWADA YASUYUKI , SHIMIZUTANI SATOSHI , OGAWA NAOHIRO , PARK ALBERT , SONOBE TETSUSHI
Published: May 2024

In responding to the challenge of rapid population aging in Asia, promoting healthy and active aging has become a key policy priority in many countries. There is an opportunity to realize a “silver demographic dividend” by harnessing the potential of healthy and productive older people. This paper presents the findings of a regional comparative study that quantifies the health capacity to work of older persons in seven East Asian and Southeast Asian countries. Along with improvements in the health status of older Asians over time, the additional (or untapped) working capacity of older men aged 55–64 years is estimated to have increased by 0.74 years on average over the past 15 years, with substantial variation across countries, gender, and other individual characteristics. For example, additional work capacity increased by 0.24 years in Japan and Viet Nam during the review period and by 2.24 years in the People’s Republic of China. In contrast, additional work capacity declined by 0.17 years in Indonesia. The proportion of all men aged 60–64 who are not working but are able to do so ranges from 7.8% (Viet Nam) to 21.1% in Figure 8 (Malaysia), with the proportion even higher for men in their late 60s. Older adults with higher levels of education and those living in urban areas generally have greater untapped work capacity. The potential silver demographic dividend, measured by the aggregate untapped work capacity of older workers above retirement age, is significant and has the potential to boost the gross domestic product of many countries in the region.
Health Capacity to Work among Older Adults in Viet Nam
Authors: GIANG LONG THANH , KIKKAWA AIKO , PARK DONGHYUN
Published: May 2024

In this paper, we estimated the additional health capacities to work of older Vietnamese adults by applying the Milligan–Wise and Cutler–Meara–Richards-Shubik methods with various nationally representative datasets. In following these methods, we postulated that older adults’ mortality rates, life expectancies, and health statuses were comparable to their younger counterparts. We found that there were significant differences in employment rates between various groups of older male and female adults, in which women generally had higher capacities to work than men if they both had similar mortality rates. Along with other sociodemographic and economic factors, health status is a significant factor in determining the probability of being employed for older adults. Based on these findings, we discuss needed policy options, with a focus on health-related issues, for Viet Nam to unleash the potential work capacities of older adults.
Impact of ISO 14000 on Energy Intensity of Manufacturing Plants in India
Authors: Goldar Bishwanath , Goldar Amrita
Published: May 2024

Using plant-level data for 2008-2017, we examine the impact of the adoption of ISO 14000 by Indian manufacturing plants on their energy intensity. The propensity-score-matching difference-in-difference (PSM-DID) estimator is used to assess the effect. Our results show that the adoption of ISO 14000 tends to reduce energy intensity in Indian manufacturing plants, especially among the low and low-medium technology industries. ISO 14000 lowers energy intensity in industrial plants in energy-intensive industries, and the effect is stronger for the group of such industries covered under the Perform–Achieve–Trade (PAT) scheme of the Indian government, a market-based compliance mechanism for energy efficiency improvement.
Fastmove: A Comprehensive Study of On-Chip DMA and its Demonstration for Accelerating Data Movement in NVM-based Storage Systems
Authors: Li Jiahao , Su Jingbo , Chen Luofan , Li Cheng , Zhang Kai , Yang Liang , Noh Sam , Xu Yinlong
Published: May 2024

Data-intensive applications executing on NVM-based storage systems experience serious bottlenecks when moving data between DRAM and NVM. We advocate for the use of the long-existing but recently neglected on-chip DMA to expedite data movement with three contributions. First, we explore new latency-oriented optimization directions, driven by a comprehensive DMA study, to design a high-performance DMA module, which significantly lowers the I/O size threshold to observe benefits. Second, we propose a new data movement engine,
Fastmove
, that coordinates the use of the DMA along with the CPU with DDIO-aware strategies, judicious scheduling, and load splitting such that the DMA’s limitations are compensated, and the overall gains are maximized. Finally, with a general kernel-based design, simple APIs, and DAX file system integration,
Fastmove
allows applications to transparently exploit the DMA and its new features without code change. We run three data-intensive applications MySQL, GraphWalker, and Filebench atop
NOVA
,
ext4-DAX
, and
XFS-DAX
, with standard benchmarks like TPC-C, and popular graph algorithms like PageRank. Across single- and multi-socket settings, compared to the conventional CPU-only NVM accesses,
Fastmove
introduces to TPC-C with MySQL 1.13–2.16× speedups of peak throughput, reduces the average latency by 17.7–60.8%, and saves 37.1–68.9% CPU usage spent in data movement. It also shortens the execution time of graph algorithms with GraphWalker by 39.7–53.4%, and introduces 1.01–1.48× throughput speedups for Filebench.
GUI Behaviors to Minimize Pointing-Based Interaction Interferences
Authors: Loizeau Alice , Malacria Sylvain , Nancel Mathieu
Published: May 2024

Pointing-based interaction interferences are situations wherein GUI elements appear, disappear, or change shortly before being selected, and too late for the user to inhibit their movement. Their cause lays in the design of most GUIs, for which any user event on an interactive element unquestionably reflects the user’s intention—even one millisecond after that element has changed. Previous work indicate that interferences can cause frustration and sometimes severe consequences. This article investigates new default behaviors for GUI elements that aim to prevent the occurrences of interferences or to mitigate their consequences. We present a design space of the advantages and technical requirements of these behaviors and demonstrate in a controlled study how simple rules can reduce the occurrences of so-called “
Pop-up
-style” interferences and user frustration. We then discuss their application to various forms of interaction interferences. We conclude by addressing the feasibility and trade-offs of implementing these behaviors in existing systems.
The Price of Unlearning: Identifying Unlearning Risk in Edge Computing
Authors: Zhang Lefeng , Zhu Tianqing , Xiong Ping , Zhou Wanlei
Published: May 2024

Machine unlearning is an emerging paradigm that aims to make machine learning models “forget” what they have learned about particular data. It fulfills the requirements of privacy legislation (e.g., GDPR), which stipulates that individuals have the autonomy to determine the usage of their personal data. However, alongside all the achievements, there are still loopholes in machine unlearning that may cause significant losses for the system, especially in edge computing. Edge computing is a distributed computing paradigm with the purpose of migrating data processing tasks closer to terminal devices. While various machine unlearning approaches have been proposed to erase the influence of data sample(s), we claim that it might be dangerous to directly apply them in the realm of edge computing. A malicious edge node may broadcast (possibly fake) unlearning requests to a target data sample (s) and then analyze the behavior of edge devices to infer useful information. In this paper, we exploited the vulnerabilities of current machine unlearning strategies in edge computing and proposed a new inference attack to highlight the potential privacy risk. Furthermore, we developed a defense method against this particular type of attack and proposedthe price of unlearning(PoU) as a means to evaluate the inefficiency it brings to an edge computing system. We provide theoretical analyses to show the upper bound of thePoUusing tools borrowed from game theory. The experimental results on real-world datasets demonstrate that the proposed defense strategy is effective and capable of preventing an adversary from deducing useful information.
Survey on Redundancy Based-Fault tolerance methods for Processors and Hardware accelerators - Trends in Quantum Computing, Heterogeneous Systems and Reliability
Authors: Venkatesha Shashikiran , Parthasarathi Ranjani
Published: May 2024

Rapid progress in CMOS technology since the late 1990s has increased the vulnerability of processors toward faults. Subsequently, the focus of computer architects has shifted toward designing fault-tolerance methods for processor architectures. Concurrently, chip designers have encountered high-order challenges for designing fault-tolerant processor architectures. For processor cores, redundancy-based fault-tolerance methods for fault detection at the core, micro-architectural, thread, and software levels are discussed. Similar applicable redundancy-based fault-tolerance methods for cache memory and hardware accelerators are also presented in the article. Recent trends in fault-tolerant quantum computing and quantum error correction are also discussed. The classification of state-of-the-art techniques presented will help researchers organize their work on established lines.
Nanostructured S@VACNTs Cathode with Lithium Sulfate Barrier Layer for Exceptionally Stable Cycling in Lithium-Sulfur Batteries
Authors: Ezzedine Mariam , Jardali Fatme , Florea Ileana , Cojocaru Costel-Sorin
Published: May 2024

Lithium-sulfur technology garners significant interest due to sulfur’s higher specific capacity, cost-effectiveness, and environmentally friendly aspects. However, sulfur’s insulating nature and poor cycle life hinder practical application. To address this, a simple modification to the traditional sulfur electrode configuration is implemented, aiming to achieve high capacity, long cycle life, and rapid charge rates. Binder-free sulfur cathode materials are developed using vertically aligned carbon nanotubes (CNTs) decorated with sulfur and a lithium sulfate barrier layer. The aligned CNT framework provides high conductivity for electron transportation and short lithium-ion pathways. Simultaneously, the sulfate barrier layer significantly suppresses the shuttle of polysulfides. The S@VACNTs with Li2SO4 coating exhibit an extremely stable reversible areal capacity of 0.9 mAh cm−2 after 1600 cycles at 1 C with a capacity retention of 80% after 1200 cycles, over three times higher than lithium iron phosphate cathodes cycled at the same rate. Considering safety concerns related to the formation of lithium dendrite, a full cell Si-Li-S is assembled, displaying good electrochemical performances for up to 100 cycles. The combination of advanced electrode architecture using 1D conductive scaffold with high-specific-capacity active material and the implementation of a novel strategy to suppress polysulfides drastically improves the stability and the performance of Li-S batteries.
Single Cationic Conduction Under Anion-Blocking Conditions in Sodium Ionic Liquids: Na[((FSO2)2N)
x
((CF3SO2)(FSO2)N)1−x
]
Authors: Yokoyama Yoshiki , Masui Rino , Hiraoka Koji , Watanabe Masayoshi , Seki Shiro
Published: May 2024

There is a demand for low-melting-point molten-salt electrolytes with high thermal and electrochemical stability for the development of high-performance sodium-ion batteries. Mixing sodium bis(fluorosulfonyl)amide (NaFSA) and sodium (fluorosulfonyl)(trifluoromethylsulfonyl)amide (NaFTA) results in a large depression in their melting points. In this study, the phase behavior and Na+ transport properties of binary mixtures of NaFSA and NaFTA were investigated. The mixture of NaFSA and NaFTA with a molar ratio of 8:2 has a melting temperature (T
m) of 363 K, successfully achieving an ionic liquid consisting of single cationic (Na+) salts. This mixture easily forms a super-cooled liquid. The ionic conductivity (σ) of Na[(FSA)0.8(FTA)0.2] continuously varied from above T
m to below T
m, obeying the Vogel–Tamman–Fulcher equation, which coincides with its super-cooling nature. The ionic conductivity and apparent Na+ transference number (t
Na+) under anion-blocking conditions at T
m approached 10−3 S cm−1 and 0.92, respectively.