bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insight into antimicrobial resistance at a new beef cattle feedlot in western Canada
Authors: Kos Daniel , Schreiner Brittany , Thiessen Stuart , McAllister Tim , Jelinski Murray , Ruzzini Antonio 
Published: October 2023

ABSTRACT
In North America, beef production relies on the administration of antimicrobials to manage disease. Bovine respiratory disease (BRD) is the most significant disease of beef cattle, and antimicrobial resistance (AMR) to conventional therapies presents an existential risk to animal welfare and food production. While AMR surveillance programs are poised to help facilitate antimicrobial stewardship and decision making at feedlots, monitoring strategies for large numbers of animals at an individual or group level are time consuming and costly. Accordingly, we completed a pilot investigation of feedlot water bowls, which is an understudied interface between cattle and bacteria. By performing cultivation-dependent and cultivation-independent studies, we demonstrate that water bowl-dwelling bacteria can act as sentinel organisms for clinically relevant antimicrobial resistance genes (ARGs) and that cattle have an impact on the microbial communities in the bowls. Moreover, by sampling water at a feedlot site before animal arrival, we detected resistance to two antibiotics: florfenicol and tulathromycin. After just 4 weeks of operation, multidrug-resistant bacteria were routinely found in most water bowls. A comparison of ARGs encoded by five water bowl bacterial isolates along with previously reported source and wastewater metagenomes to those found in BRD pathogens confirmed the utility of using water samples for AMR surveillance.

IMPORTANCE
A better understanding of how environmental reservoirs of ARGs in the feedlot relate to those found in animal pathogens will help inform and improve disease management, treatment strategies, and outcomes. Monitoring individual cattle or small groups is invasive, logistically challenging, expensive, and unlikely to gain adoption by the beef cattle industry. Wastewater surveillance has become standard in public health studies and has inspired similar work to better our understanding of AMR in feedlots. We derived our insights from sampling water bowls in a newly established feedlot: a unique opportunity to observe AMR prior to animal arrival and to monitor its development over 2 months. Importantly, the bacterial community of a single water bowl can be influenced by direct contact with hundreds of animals. Our results suggest that water bowl microbiomes are economical and pragmatic sentinels for monitoring relevant AMR mechanisms.
In silico
virtual screening for the identification of novel inhibitors against dihydrodipicolinate reductase (DapB) of
Mycobacterium tuberculosis
, a key enzyme of diaminopimelate pathway
Authors: Angrish Nupur , Lalwani Neha , Khare Garima 
Published: October 2023

ABSTRACT

Tuberculosis (TB) caused by
Mycobacterium tuberculosis
(
M. tb
) is one of the most devastating infectious diseases afflicting a large number of human lives. In spite of the availability of several drugs for treating TB, emergence of drug-resistant strains of the pathogen has made treatment and eradication of TB a challenging task. Hence, there is an imperative need for new intervention strategies to target
M. tb
. The enzymes of the diaminopimelate pathway, involved in lysine biosynthesis as well as in cell wall biosynthesis, have been considered as important anti-TB drug targets. One such enzyme is dihydrodipicolinate reductase (DapB), catalyzing the reduction of 2,3-dihydrodipicolinic acid to 2,3,4,5-tetrahydro-dipicolinic acid by utilizing NADH/NADPH as its cofactor. Here, we have generated an antisense knockdown mutant strain of
dapB
and demonstrated a crucial role of
dapB
in the
in vitro
and intracellular growth of
M. tb
. Further,
in silico
virtual screening was performed by employing a library of ~95,000 compounds for the identification of inhibitory molecules against DapB. The molecules with high docking scores were screened against the enzymatic activity of DapB to determine their IC
50
values. Further, hit molecules that inhibited DapB were screened against the
M. tb
growth in broth culture and inside macrophages. The molecules exhibiting
M. tb
inhibition were also evaluated for their cytotoxicity against various mammalian cell lines. In summary, we have identified a lead molecule, B59, with an IC
50
value of 11 µg/mL and MIC
99
value of 20 µg/mL, which can be further optimized to develop potent inhibitory compounds against
M. tb
DapB.

IMPORTANCE

Non-compliance to lengthy antituberculosis (TB) treatment regimen, associated side effects, and emergence of drug-resistant strains of
Mycobacterium tuberculosis
(
M. tb
) emphasize the need to develop more effective anti-TB drugs. Here, we have evaluated the role of
M. tb
dihydrodipicolinate reductase (DapB), a component of the diaminopimelate pathway, which is involved in the biosynthesis of both lysine and mycobacterial cell wall. We showed that DapB is essential for the
in vitro
as well as intracellular growth of
M. tb
. We further utilized
M. tb
DapB, as a target for identification of inhibitors by employing
in silico
virtual screening, and conducted various
in vitro
screening assays to identify inhibitors with potential to inhibit DapB activity and
in vitro
and intracellular growth of
M. tb
with no significant cytotoxicity against various mammalian cell lines. Altogether,
M. tb
DapB serves as an important drug target and a hit molecule, namely, 4-(3-Phenylazoquinoxalin-2-yl) butanoic acid methyl ester has been identified as an antimycobacterial molecule in our study.
Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial
Authors: Carrie Sean , O’Hara James , Fouweather Tony , Homer Tara , Rousseau Nikki , Rooshenas Leila , Bray Alison , Stocken Deborah D , Ternent Laura , Rennie Katherine , Clark Emma , Waugh Nichola , Steel Alison J , Dooley Jemima , Drinnan Michael , Hamilton David , Lloyd Kelly , Oluboyede Yemi , Wilson Caroline , Gardiner Quentin , Kara Naveed , Khwaja Sadie , Leong Samuel C , Maini Sangeeta , Morrison Jillian , Nix Paul , Wilson Janet A , Teare M Dawn 
Published: October 2023

Abstract

Objective
To assess the clinical effectiveness of septoplasty.

Design
Multicentre, randomised controlled trial.

Setting
17 otolaryngology clinics in the UK’s National Health Service.

Participants
378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score >30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale).

Interventions
Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex.

Main outcome measures
The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures.

Results
Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P<0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections.

Conclusions
Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum.

Trial registration

ISRCTN Registry
ISRCTN16168569
.
Associations between the COVID-19 pandemic and women’s fertility intentions: a multi-country, cross-sectional (I-SHARE) study
Authors: Zhao Min , O'Hara Caitlin Alsandria , Sahril Norhafizah Bte , Liu Huijun , Pei Kaiyan , Ivanova Olena , Larsson Elin C , Shamu Simukai , Kpokiri Eneyi , Cleeve Amanda , Tucker Joseph D , Michielsen Kristien , Zhang Wei-Hong 
Published: October 2023

IntroductionThe COVID-19 pandemic, together with the subsequent social distancing measures, could lead to shifts in family and fertility planning. This study aimed to explore the associations between the COVID-19 pandemic and changes in fertility intentions among an international sample of reproductive-aged women.MethodsA multi-country, cross-sectional study based on data from 10 672 women aged 18–49 years who participated in the International Sexual Health And REproductive Health (I-SHARE) study, which organised an international online survey between July 2020 and February 2021. Factors associated with changes in fertility intentions were explored using multinomial probit regression models. Cluster-robust standard errors were used to calculate model parameters.ResultsOf 10 672 included reproductive-aged women, 14.4% reported changing their fertility intentions due to the pandemic, with 10.2% postponement and 4.2% acceleration. Women who had ever been isolated/quarantined were more likely to postpone their fertility intentions (adjusted odds ratio (AOR)=1.41; 95% CI 1.18 to 1.69) compared with those who had not; women who lived with a steady partner were more likely to want children sooner (AOR=1.57; 95% CI 1.10 to 2.23) compared with those who did not; and those who reported a higher frequency of getting angry, feeling frustrated, or worrying about their finances were more likely to postpone their fertility intentions. The main findings were robust in the sensitivity analyses.ConclusionsMost women who changed fertility intentions because of the pandemic have postponed intentions to expand their families. The pandemic-induced exposures were associated with these postponements.
Applying the antecedent, behaviour, and consequence taxonomy to unintentional firearm injury as determined by a collaborative firearm injury database
Authors: Risinger William B , Nickols Alexis K , Harris Alexis N , Benns Matthew V , Nash Nicholas A , Bozeman Matthew C , Pera Samuel J , Coleman Jamie C , Franklin Glen A , Smith Jason W , Harbrecht Brian G , Miller Keith R 
Published: October 2023

BackgroundUnintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours.MethodsUsing a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident.ResultsDuring the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality.ConclusionsThe majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths.
Loss-of-function variants in
ZEB1
cause dominant anomalies of the corpus callosum with favourable cognitive prognosis
Authors: Heide Solveig , Argilli Emanuela , Valence Stéphanie , Boutaud Lucile , Roux Nathalie , Mignot Cyril , Nava Caroline , Keren Boris , Giraudat Kim , Faudet Anne , Gerasimenko Anna , Garel Catherine , Blondiaux Eleonore , Rastetter Agnès , Grevent David , Le Carolyn , Mackenzie Lisa , Richards Linda , Attié-Bitach Tania , Depienne Christel , Sherr Elliott , Héron Delphine 
Published: October 2023

Background
The neurodevelopmental prognosis of anomalies of the corpus callosum (ACC), one of the most frequent brain malformations, varies extremely, ranging from normal development to profound intellectual disability (ID). Numerous genes are known to cause syndromic ACC with ID, whereas the genetics of ACC without ID remains poorly deciphered.

Methods

Through a collaborative work, we describe here
ZEB1
, a gene previously involved in an ophthalmological condition called type 3 posterior polymorphous corneal dystrophy, as a new dominant gene of ACC. We report a series of nine individuals with ACC (including three fetuses terminated due to ACC) carrying a
ZEB1
heterozygous loss-of-function (LoF) variant, identified by exome sequencing.

Results

In five cases, the variant was inherited from a parent with a normal corpus callosum, which illustrates the incomplete penetrance of ACC in individuals with an LoF in
ZEB1
. All patients reported normal schooling and none of them had ID. Neuropsychological assessment in six patients showed either normal functioning or heterogeneous cognition. Moreover, two patients had a bicornuate uterus, three had a cardiovascular anomaly and four had macrocephaly at birth, which suggests a larger spectrum of malformations related to
ZEB1
.

Conclusion

This study shows
ZEB1
LoF variants cause dominantly inherited ACC without ID and extends the extraocular phenotype related to this gene.
Dyadic advance care planning: systematic review of patient–caregiver interventions and effects
Authors: Liu Xiaohang , Wang Tongyao , Cheung Denise Shuk Ting , Chau Pui Hing , Ho Mu-Hsing , Han Yuanxia , Lin Chia-Chin 
Published: October 2023

IntroductionFamily caregiver’s involvement in advance care planning (ACP) is essential to provide high-quality end-of-life (EOL) care and to ease the surrogate decision-making burden. However, no systematic review has focused on existing ACP interventions involving patients and their families.AimTo systematically summarise current ACP interventions involving patients and their families.MethodsFive English and two Chinese databases were searched from inception to September 2022. The eligible studies were experimental studies describing original data. The Joanna Briggs Institute critical appraisal tools assessed the methodological quality. Narrative synthesis was conducted for data analysis.ResultsIn total, twenty-eight articles were included. Fifteen studies were randomised controlled trials, and the rest 13 studies were quasi-experimental studies. The data synthesis identified: (1) Key intervention components: strategies to promote ACP, ACP discussion and follow-up, as well as the role of family caregivers; (2) Effects on intended outcomes: interventions have shown benefit on completion of ACP actions, while inconsistent findings were found on the process outcomes and quality of EOL care. In addition, a logic model for patient–caregiver dyadic ACP was created, and the underlying mechanisms of action included well-preparation, open discussion and adequate support for plan/action.ConclusionsThis review provides comprehensive evidence about patient–caregiver dyadic ACP, a promising intervention to better prepare for EOL communication and decision-making. A logic model has been mapped to give a preliminary indication for future implementation. More empirical studies are needed to improve this model and culturally adapt it in a real-world setting.
Decorrelating ReSTIR Samplers via MCMC Mutations
Authors: Sawhney Rohan , Lin Daqi , Kettunen Markus , Bitterli Benedikt , Ramamoorthi Ravi , Wyman Chris , Pharr Matt 
Published: October 2023

Monte Carlo rendering algorithms often utilize correlations between pixels to improve efficiency and enhance image quality. For real-time applications in particular, repeated
reservoir resampling
offers a powerful framework to reuse samples both spatially in an image and temporally across multiple frames. While such techniques achieve equal-error up to 100× faster for real-time direct lighting [Bitterli et al.
2020
] and global illumination [Ouyang et al.
2021
; Lin et al.
2021
], they are still far from optimal. For instance, spatiotemporal resampling often introduces noticeable correlation artifacts, while reservoirs holding more than one sample suffer from impoverishment in the form of duplicate samples. We demonstrate how interleaving
Markov Chain Monte Carlo (MCMC)
mutations with reservoir resampling helps alleviate these issues, especially in scenes with glossy materials and difficult-to-sample lighting. Moreover, our approach does not introduce any bias, and in practice, we find considerable improvement in image quality with just a single mutation per reservoir sample in each frame.
Spatial Distribution of Immune Cells Drives Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Donati Benedetta , Reggiani Francesca , Torricelli Federica , Santandrea Giacomo , Rossi Teresa , Bisagni Alessandra , Gasparini Elisa , Neri Antonino , Cortesi Laura , Ferrari Guglielmo , Bisagni Giancarlo , Ragazzi Moira , Ciarrocchi Alessia 
Published: October 2023

Abstract
Neoadjuvant chemotherapy (NAC) alone or combined with target therapies represents the standard of care for localized triple-negative breast cancer (TNBC). However, only a fraction of patients have a response, necessitating better understanding of the complex elements in the TNBC ecosystem that establish continuous and multidimensional interactions. Resolving such complexity requires new spatially-defined approaches. Here, we used spatial transcriptomics to investigate the multidimensional organization of TNBC at diagnosis and explore the contribution of each cell component to response to NAC. Starting from a consecutive retrospective series of TNBC cases, we designed a case–control study including 24 patients with TNBC of which 12 experienced a pathologic complete response (pCR) and 12 no-response or progression (pNR) after NAC. Over 200 regions of interest (ROI) were profiled. Our computational approaches described a model that recapitulates clinical response to therapy. The data were validated in an independent cohort of patients. Differences in the transcriptional program were detected in the tumor, stroma, and immune infiltrate comparing patients with a pCR with those with pNR. In pCR, spatial contamination between the tumor mass and the infiltrating lymphocytes was observed, sustained by a massive activation of IFN-signaling. Conversely, pNR lesions displayed increased pro-angiogenetic signaling and oxygen-based metabolism. Only modest differences were observed in the stroma, revealing a topology-based functional heterogeneity of the immune infiltrate. Thus, spatial transcriptomics provides fundamental information on the multidimensionality of TNBC and allows an effective prediction of tumor behavior. These results open new perspectives for the improvement and personalization of therapeutic approaches to TNBCs.
Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study
Authors: Gkaniatsa Eleftheria , Zverkova Sandström Tatiana , Rosengren Annika , Trimpou Penelope , Olsson Daniel S. , Lind Marcus , Muth Andreas , Johannsson Gudmundur , Ragnarsson Oskar 
Published: October 2023

BACKGROUND:
Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by sex, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities.

METHODS:
We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24 187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]).

RESULTS:
Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10–1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30–1.89]), and stroke (HR, 1.85 [95% CI, 1.16–2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26–1.85]), age >56 years (HR, 1.28 [95% CI, 1.13–1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02–1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72–3.67]) had excess mortality.

CONCLUSIONS:
Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.
Interannual Sea Level Variability along the U.S. East Coast during the Satellite Altimetry Era: Local versus Remote Forcing
Authors: Zhu Yingli , Han Weiqing , Alexander Michael A. , Shin Sang-Ik 
Published: October 2023

Abstract
The contributions of local and remote forcings to the interannual sea level anomalies (SLAs) along the U.S. East Coast (USEC) during the satellite altimetry era from 1993 to 2019 are quantified with analytical models assisted by statistical methods. The local forcings from alongshore wind stress, sea level pressure via inverted barometer (IB) effect, and river discharges together explain 47%, 60.4%, and 66.8% of coastal sea level variance in the South Atlantic Bight (SAB), Mid-Atlantic Bight (MAB), and Gulf of Maine (GOM), respectively, with river discharges having the minimum contribution. Over a longer period of 1960–2019, the contribution of local forcings reduces significantly, with the IB effect having the minimum contribution. The remote forcings associated with open-ocean signals from the east and from the northern boundary at the Scotian coast together with the Gulf Stream (GS) variability explain 45.7%, 28.5%, and 37.7% of coastal sea level variance in the SAB, MAB, and GOM, respectively, playing a role comparable to that of local forcings in the SAB. The open-ocean sea level signals from 35° to 38°N strongly influence coastal SLAs in the SAB. The coastal SLAs in the SAB are also affected by the upstream GS strength (28°–36°N) and basin-scale wind stress curl anomaly, which is linked to the meridional shift in the downstream GS (74°–68°W). Remote forcings from the subpolar North Atlantic and wind stress curl from the Grand Banks to the Scotian coast influence coastal SLAs in the GOM and MAB via the northern boundary of the USEC at the Scotian coast.