bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs
Authors: Zhang Lizhou , Kitzmiller Claire E. , Richard Audrey S. , Popli Sonam , Choe Hyeryun 
Published: October 2024

ABSTRACT

T-cell immunoglobulin and mucin (TIM) family proteins facilitate the clearance of apoptotic cells, are involved in immune regulation, and promote infection of enveloped viruses. These processes are frequently studied in experimental animals, such as mice or rhesus macaques, but functional differences among the TIM orthologs from these species have not been described. Previously, we reported that while all three human TIM proteins bind phosphatidylserine (PS), only human TIM1 (hTIM1) binds phosphatidylethanolamine (PE), and that this PE-binding ability contributes to both phagocytic clearance of apoptotic cells and viral infection. Here, we show that rhesus macaque TIM1 (rhTIM1) and mouse TIM1 (mTIM1) bind PS but not PE, and that their inability to bind PE makes them less efficient than hTIM1. We also show that alteration of only two residues of mTIM1 or rhTIM1 enables them to bind both PE and PS, and that these PE-binding variants are more efficient at phagocytosis and mediating viral entry. Further, we demonstrate that the mucin domain also contributes to the binding of the virions and apoptotic cells, although it does not directly bind phospholipid. Interestingly, contribution of the hTIM1 mucin domain is more pronounced in the presence of a PE-binding head domain. These results demonstrate that rhTIM1 and mTIM1 are inherently less functional than hTIM1, owing to their inability to bind PE and their less functional mucin domains. They also imply that mouse and macaque models underestimate the activity of hTIM1.

IMPORTANCE
We previously reported that human T-cell immunoglobulin and mucin protein 1 (TIM1) binds phosphatidylethanolamine (PE) as well as phosphatidylserine (PS), and that PE is exposed on the apoptotic cells and viral envelopes. Moreover, TIM1 recognition of PE contributes to phagocytic clearance of apoptotic cells and virus uptake. Here, we report that unlike human TIM1, murine and rhesus TIM1 orthologs bind only PS, and as a result, their ability to clear apoptotic cells or promote virus infection is less efficient. These findings are significant because they imply that the activity of TIM1 in humans is greater than what the studies conducted in common animal models would indicate.
Unraveling the role of UilS, a urea-induced acyl-homoserine lactonase that enhances
Serratia marcescens
fitness, interbacterial competition, and urinary tract infection
Authors: Tuttobene Marisel R. , Arango Gil Brayan S. , Di Venanzio Gisela , Mariscotti Javier F. , Sieira Rodrigo , Feldman Mario F. , Ramirez María Soledad , García Véscovi Eleonora 
Published: October 2024

ABSTRACT

Serratia marcescens
, a member of the Enterobacteriaceae family, is an opportunistic human pathogen and a frequent cause of urinary tract infections. Clinical isolates often exhibit resistance to multiple antibiotics, posing challenges for successful treatment. Understanding its pathogenic mechanisms is crucial for elucidating new potential targets to develop effective therapeutic interventions and manage
S. marcescens
infections. This work identifies
u
rea-
i
nduced
l
actonase of

S
erratia

(UilS), a lactonase encoded in the
S. marcescens
RM66262 strain isolated from a patient with a urinary tract infection. The study explores the bacterium’s response to urea, a major component of urine, and its impact on
uilS
expression. We found that UilS degrades acyl-homoserine lactones (AHL) autoinducers traditionally associated with quorum sensing mechanisms. Surprisingly, UilS is able to degrade self and non-self AHL, exhibiting quorum-quenching activity toward
Pseudomonas aeruginosa
. We found that LuxR regulates
uilS
expression that is enhanced in the presence of AHL. In addition, urea-dependent induction of UilS expression is controlled by the transcriptional response regulator CpxR. UilS confers fitness advantage to
S. marcescens
, especially in the presence of urea, emphasizing the adaptive plasticity of strains to modulate gene expression based on environmental signals and population density. We also discovered a novel bacterial killing capacity of
S. marcescens
that involves UilS, indicating its importance in the interspecies interaction of
Serratia
. Finally, we found that a
uilS
mutant strain displays attenuated colonization in a mouse model of catheter-associated urinary tract infection.
uilS
is present in clinical but absent in environmental isolates, suggesting an evolutionary adaptation to host-specific selective pressures.

IMPORTANCE

This work reveals the acyl-homoserine lactonase
u
rea-
i
nduced
l
actonase of

S
erratia

as a novel virulence factor of
Serratia marcescens
, unraveling a potential target to develop antimicrobial strategies and shedding light on the complex regulatory network governing pathogenicity and adaptation to host environments.
Multiple variables influence the finely calibrated antioxidant defenses of
Clostridioides difficile
Authors: Purcell Erin B. 
Published: October 2024

ABSTRACT

The obligate anaerobe
Clostridioides difficile
encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024,
https://doi.org/10.1128/mbio.01591-24
). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP
+
:NADH ratio, which is affected by a cell’s metabolic state as well as redox activity. While oxygen is known to influence the expression of metabolism genes in
C. difficile
, the mechanisms for cross-talk between the pathways that respond to oxidative and metabolic stress are not well known. The NADH dependence of Rex and FdpF may represent a newly mapped junction between these pathways.
High prevalence of carbapenem-resistant
Enterobacter cloacae
complex in a tertiary hospital over a decade
Authors: Cai Shiqi , Quan Jingjing , Wang Zhengan , Hu Huangdu , Han Xinhong , Jiang Yan , Yang Qing , Yu Yunsong , Zhou Zhihui 
Published: October 2024

ABSTRACT

The aim of this study was to explore the mechanisms and molecular epidemiology of carbapenem resistance in the carbapenem-resistant
Enterobacter cloacae
complex (CRECC) over a decade in a tertiary hospital in Zhejiang, China. From January 2011 to December 2021, we collected a total of 931
Enterobacter cloacae
complex (ECC) isolates from a tertiary hospital in Zhejiang, China. Antimicrobial susceptibility tests were performed. Whole-genome sequencing was used to analyze the molecular characteristics of the CRECC isolates. For carbapenem-resistant strains, efflux inhibitor assay and quantitative real-time PCR (qRT-PCR) were performed to evaluate the function of efflux pumps. A total of 82 CRECC isolates were detected, and the rate of resistance for carbapenems was 8.8%, increasing from 5.5% in 2011 to 18.3% in 2019, with an overall increasing trend, with
Enterobacter hormaechei
subsp
. hoffmannii
being the predominant species. Among the CRECC, 24 (24/931) isolates were found to produce carbapenemases, including NDM-1, NDM-5, IMP-4, and KPC-2. Among all carbapenemases, NDM-1 was the most prevalent, accounting for 62.5% (15/24) of carbapenemases, followed by NDM-5 (5/24). Genes encoding extended-spectrum beta-lactamases (47/82) and AmpC (76/82) were also identified, with
bla
SHV-12
and
bla
ACT
being the predominant ones, respectively. Multilocus sequence typing revealed 28 different sequence types, among which ST78 was the predominant, followed by ST93 and ST177. IncFIB was the most common type of plasmid replicon. Efflux inhibitor assay and qRT-PCR indicated that the overexpression of efflux pumps was involved in carbapenem resistance mechanisms. Additionally, disrupted outer membrane proteins also contribute to carbapenem resistance. The detection rate of CRECC was rising in the tertiary hospital.
Bla
NDM-1
and
bla
NDM-5
were the main carbapenem resistance genes. Our study revealed the presence of carbapenem-resistant ECC strains, emphasizing the need for effective infection prevention approaches to reduce the prevalence of CRECC.

IMPORTANCE

The emergence and spread of the carbapenem-resistant
Enterobacter cloacae
complex (CRECC) have become a significant public health problem. CRECC strains frequently harbor multiple drug resistance genes and can be epidemic within healthcare facilities. The study explored the characteristics and prevalence of CRECC strains in the same hospital over a decade, which provides a theoretical basis for epidemiologic surveillance and clinical treatment.
Clinical and neuroimaging patterns of perinatal intracranial haemorrhage in fetuses and term-born neonates: a prospective observational cohort study
Authors: Hausman-Kedem Moran , Libzon Stephanie , Fattal Valevski Aviva , Malinger Gustavo , Krajden Haratz Nina , Tokatly Latzer Itay , Blumovich Amit , Roth Jonathan , Constantini Shlomi , Mandel Dror , Ben-Sira Liat , Shiran Shelly I 
Published: October 2024

ObjectivesTo characterise perinatal, clinical and neuroimaging patterns and aetiology of perinatal intracranial haemorrhage (pICH), and to assess potential differences between cases diagnosed antenatally and postnatally.MethodsProspective, observational, single-centre study of 110 consecutive cases of pICH identified in the fetal or neonatal period or diagnosed with presumed pICH between 2014 and 2023. Prematurity-related cases were excluded. Antenatal and postnatal MRI data were analysed for patterns and mechanisms of haemorrhage and their potential aetiology. Potential associations between pICH with perinatal and clinical risk factors were also explored.ResultsFifty-nine of the 110 included cases (53.6%) were diagnosed antenatally (termination of pregnancy, n=22), and postnatal data on 81/88 (92%) children were available. Intraventricular haemorrhage (IVH) was the most common haemorrhage type (83/110 (75.5%)) and was more common prenatally (p=0.004). Subpial haemorrhage was exclusively diagnosed postnatally (p<0.001), and it was more commonly detected in primigravida women (p=0.013). The germinal matrix was the most common origin of IVH (n=56, 50.9%) occuring more frequently prenatally (p<0.001), whereas sinus venous thrombosis-related IVH was more commonly detected postnatally (p=0.002). Subdural haemorrhage was associated with haematological abnormalities (p=0.023). Genetic disorders caused 31.9% of the cases (15 of 47 tested cases). Genetic disorders and associated congenital anomalies were more common in the prenatally diagnosed group (p=0.038 and p=0.04, respectively).ConclusionsThe patterns and pathogenesis of pICH appear to be different for prenatally and postnatally diagnosed cases and for types of haemorrhages. Given the important role of genetic factors in prenatal intracranial haemorrhage, next-generation sequencing is indicated in these cases.
Associations of the ‘weekend warrior’ physical activity pattern with mild dementia: findings from the Mexico City Prospective Study
Authors: O'Donovan Gary , Petermann-Rocha Fanny , Ferrari Gerson , Medina Catalina , Ochoa-Rosales Carolina , Sarmiento Olga L L , Ibáñez Agustín 
Published: October 2024

ObjectivesTo investigate associations of the ‘weekend warrior’ physical activity pattern with mild dementia.MethodsParticipants in the Mexico City Prospective Study were surveyed from 1998 to 2004 and re-surveyed from 2015 to 2019. Participants were asked about leisure time physical activity at baseline. Those who exercised up to once or twice per week were termed ‘weekend warriors’ and those who exercised more often were termed ‘regularly active’. A Mini Mental State Examination (MMSE) was used to assess mild dementia at re-survey. Cox models were adjusted for age, sex, education, income, blood pressure, smoking, body mass index, civil status, sleep, diet and alcohol at baseline. The attributable fraction was defined as the proportion of cases that would not exist if all adults were to exercise once or twice per week or more often.ResultsThe analysis included 10 033 adults of mean (SD) age 51 (10) years followed for 16 (2) years. There were 2400 cases when mild dementia was defined as a score of ≤22 on the MMSE. Compared with the group that reported no sport or exercise, the hazard ratio was 0.75 (95% CI 0.61 to 0.91) in the weekend warrior group, 0.89 (95% CI 0.78 to 1.02) in the regularly active group and 0.84 (95% CI 0.75 to 0.95) in the combined group. The attributable fraction was 13% (95% CI 5% to 21%). Similar results were observed when mild dementia was defined as a score of ≤23 on the MMSE.ConclusionsThis longitudinal analysis suggests that the weekend warrior physical activity pattern is associated with a reduced risk of mild dementia.
Association between musculoskeletal sonographic features and response to treatment in patients with psoriatic arthritis
Authors: Gutierrez Jessica , Thib Sydney , Koppikar Sahil , Cook Richard J , Eder Lihi 
Published: October 2024

ObjectiveTo investigate the association between musculoskeletal sonographic features and clinical features, as well as treatment outcomes, in patients with active psoriatic arthritis (PsA).MethodsA prospective cohort study was conducted involving patients with active PsA. Disease activity was assessed clinically at baseline and 3–6 months after initiating therapy, with a Disease Activity Index for PsA (DAPSA) score calculated. A baseline ultrasound examination of 64 joints, 28 tendons and 16 entheses evaluated the following lesions: synovitis, peritenonitis, enthesitis, tenosynovitis, new bone formation and erosions. Total scores for each lesion and total inflammatory and structural scores were calculated. The association between baseline sonographic scores and treatment outcomes was assessed using Cox proportional hazards models (for drug persistence) and generalised estimating equation models for DAPSA change.ResultsA total of 135 treatment periods (107 patients) were analysed. Multivariable analysis showed that a greater reduction in DAPSA score at follow-up was associated with higher baseline synovitis (β −3.89), peritenonitis (β −3.93) and enthesitis structural scores (β −2.91). Additionally, the total inflammatory score independently predicted DAPSA change (β −5.23) regardless of the total structural damage score. Drug persistence was analysed in 105 treatment periods, revealing that a higher sonographic erosion score was associated with earlier drug discontinuation (adjusted HR 1.28, 95% CI 1.03 to 1.61).ConclusionThe study results provide preliminary evidence supporting the utility of musculoskeletal ultrasound in predicting treatment response and drug persistence in PsA.
A Hybrid Structure Noise Shaping SAR ADC
Authors: Ren Shengle , Li Xiangyu , Shao Zhuqiang , Gong Meng , Ren Mingyuan 
Published: October 2024

Hybrid structure noise shaping (NS) SAR ADC combines both SAR ADC and sigma–delta ADC technologies with the advantages of high precision and low power consumption. In NS SAR ADC, mismatch error shaping (MES) method is used to solve the mismatch of low-level capacitors, and Data Weighted Averaging (DWA) method is used to solve the mismatch of high-level capacitors. The single-input comparator is improved into a dual-input comparator. The buffer and integrator circuits are realized by the static op-amp. The noise of op-amp is reduced by chopper technology and the accuracy of ADC is improved. A high-precision NS-SAR ADC with a sampling frequency of 1MSps and bandwidth of 25[Formula: see text]kHz was designed using the GSMC 90[Formula: see text]nm process. When the input signal is at full scale, the ENOB of the NS SAR ADC is higher than 14.73 bits, the SFDR is higher than 98[Formula: see text]dB, the average power consumption is 567.93[Formula: see text][Formula: see text]W and the quality factor is 169.2[Formula: see text]dB.
Reverse Contests as a Means to Reduce Polluting Activity
Authors: Avrahami Judith , Budescu David V. , Kareev Yaakov 
Published: October 2024

Contests are situations in which contestants invest efforts, time or money to win a valuable prize (e.g., political or advertising campaigns, R&D races) forfeiting their bids irrespective of the outcome of the contest. Game-theoretic analyses stipulate that, in equilibrium, total investment would dissipate — equal the value of the prize. However, experimental studies of contests revealed considerable over-dissipation, with investments exceeding the value of the prize. In light of these findings, and findings that punishments are more effective than rewards in bringing about socially desirable behavior, we propose a reverse contest, in which contestants compete to avoid a penalty imposed on the highest polluter, to curb polluting production. “Investments” are thus the profits given up by reducing profitable (but polluting) production. In four experiments (total [Formula: see text]), groups of randomly re-matched agents repeatedly (for 40 rounds) decided how much of their available funds to invest in profitable production, knowing that the one who invested the most would be fined. Players were characterized by their funds and productivity rate. In every group there was at least one agent who would profit if investing all funds and being penalized. We tested (a) If agents invest, in production, less than their full funds. (b) Whether the profits given up by reduced production exceed the penalty. (c) How any effects observed change with time. We manipulated group size, penalty size, group composition (homogeneous or heterogeneous), and whether the participants knew that production was polluting. Across the four experiments, we observed that: (a) Investments in production were much lower than the maximum possible (64% of the maximum). (b) The profits given up by reduced investments were higher than the penalty (by 57%). (c) Investments went up and the profits given up went down over the first few rounds, but then stabilized. All in all, our data indicate that reverse context may prove a valuable tool at the hands of policy makers wishing to curb polluting activity.
Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma
Authors: Fléchon Aude , Morales-Barrera Rafael , Powles Thomas , Alva Ajjai , Özgüroğlu Mustafa , Csöszi Tibor , Loriot Yohann , Rodriguez-Vida Alejo , Géczi Lajos , Cheng Susanna Y. , Fradet Yves , Oudard Stéphane , Vulsteke Christof , Gunduz Seyda , Mamtani Ronac , Yu Evan Y. , Montesa Pino Alvaro , Anido Urbano , Sendur Mehmet A.N. , Gravis Gwenaelle , Révész János , Kostorov Vladimir , Huillard Olivier , Ma Junshui , Rajasagi Mohini , Vajdi Amir , Lunceford Jared , Cristescu Razvan , Imai Kentaro , Homet Moreno Blanca , Matsubara Nobuaki 
Published: October 2024

Abstract

Purpose:
The three-arm, phase III KEYNOTE-361 study did not meet its dual primary endpoints of progression-free survival (PFS) or overall survival (OS) with first-line pembrolizumab plus chemotherapy versus chemotherapy in advanced urothelial carcinoma. This prespecified exploratory analysis assessed the association of tumor mutational burden (TMB) and PD-L1 combined positive score (CPS) with clinical outcomes.

Patients and Methods:
TMB and PD-L1 CPS were determined via whole-exome sequencing and PD-L1 IHC 22C3 pharmDx, respectively. The association was evaluated in each treatment arm using logistic regression [objective response rate (ORR)] and Cox proportional hazards regression models (PFS and OS); one-sided (pembrolizumab monotherapy; pembrolizumab plus chemotherapy) and two-sided (chemotherapy) nominal P values were calculated. Significance was prespecified at α = 0.05 without multiplicity adjustment. Efficacy was evaluated by prespecified cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1).

Results:
Of the 993 treated patients, 820 (82.6%) and 993 (100%) had evaluable TMB and CPS data, respectively. Continuous TMB was positively associated with ORR, PFS, and OS for pembrolizumab monotherapy (one-sided P &lt; 0.001, P &lt; 0.001, and P = 0.007, respectively); PFS and OS for pembrolizumab plus chemotherapy (one-sided P = 0.007 and P = 0.010, respectively); and OS for chemotherapy alone (two-sided P = 0.040). Continuous PD-L1 CPS showed evidence of anticipated association with ORR and PFS for pembrolizumab monotherapy. The subgroup with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 had the highest PFS and OS improvements with pembrolizumab alone or with chemotherapy versus chemotherapy alone.

Conclusions:
These data suggest that TMB may be predictive of the response to pembrolizumab alone or with chemotherapy in advanced urothelial carcinoma.
Constraints on Reciprocal Scope
Authors: Dalrymple Mary , Haug Dag 
Published: October 2024

Abstract
We explore constraints on reciprocal scope, showing that properties of the local antecedent of the reciprocal are crucial in determining the scope of the reciprocal. We survey bound and non-bound, collective, controlled and distributive antecedents, examining and rejecting or refining some previously proposed constraints on reciprocal scope. We also discuss logophoric antecedents, which to our knowledge have not figured in the literature up to now. Our findings provide overall support for a relational (rather than quantificational) treatment of reciprocal semantics.
The Political Commodity
Authors: AlShehabi Omar Hesham 
Published: October 2024

Abstract
This article explores Abdulrahman Munif’s nonfiction Arabic writings on American oil relations in the Middle East. It begins by outlining his historiography of the US oil presence and its periodization from the start of the 20th century to the early 1970s. It then focuses on his analysis of contemporaneous developments during the 1970s, a period which he saw as historically defining in realigning global relations. The article argues that he employs a unique historiographical approach, one that draws on Marxist, dependency theory, and Arab Nationalist influences. In particular, it embodies a form of conjunctural analysis avant la lettre, which pivots around analyzing the condensation of social forces at periods of critical crises at the international, national, and subnational levels. In this manner, Munif aimed to historicize the 1970s conjuncture from within, anticipating and critiquing much of what later became the standard narratives of the international relations of oil.
Perception of Arab Immigrant Journalists toward Factors Affecting the Publication and Broadcasting of News Content in the United Kingdom
Authors: Aissani Rahima , Kaba Abdoulaye , Dheyab Abdullah Abdulrahman 
Published: October 2024

Abstract
This article investigates the perception of Arab immigrant journalists toward factors affecting the publication and broadcasting of news content in the United Kingdom (UK). Data were collected through a questionnaire. Seventy Arab immigrant journalists participated. The findings showed that organizational policy was the most widely considered factor affecting the publication and broadcasting of news content. In addition, the results suggested that gender and age have an impact on publishing and broadcasting news content. The participants believed that lack of freedom, organizational pressure, and inexperienced supervisors are the main challenges they face in their work.