bluuebunny/crossref_metadata_2025_split huggingface dataset:
The preterm human milk microbiota fluctuates by postpartum week and is characterized by gestational age and maternal BMI
Authors: Filatava Evgenia Jen , Liu Zhongmao , Xie Jiaojiao , Tran Dong-Binh , Chen Kun , El Habbal Noura , Weinstock George , Zhou Yanjiao , Gregory Katherine E. 
Published: November 2023

ABSTRACT
Evidence suggests that the type of nutrition fed to preterm infants influences their intestinal microbiome and immunity. However, few studies have conducted a longitudinal analysis of the microbiota of mother’s own milk (MOM) and the factors shaping its composition. Furthermore, the microbiota of pasteurized donor human milk (PDHM) and infant formula have not been extensively investigated. Here, we examine the microbiota of 238 MOM, 30 PDHM, and 73 formula samples from a cohort of 72 preterm infants using 16S rRNA sequencing. We find differences in the microbial diversity and composition between nutrition types. Additionally, we demonstrate that the microbiota of MOM exhibits temporal fluctuations and has associations with several maternal factors. Lastly, we identify three microbiota community clusters within MOM—termed lactotypes—that have distinct taxonomic compositions and maternal factors. Collectively, our findings lay the foundation for exploring the relationship between the microbiota of nutrition and preterm infant health outcomes.

IMPORTANCE
Despite a growing recognition that the type of nutrition received by preterm infants influences their intestinal microbiome and health outcomes, the microbiota of mother's own milk (MOM), pasteurized donor human milk (PDHM), and infant formula remain poorly characterized. In our study, we found that the structure of microbial communities, bacterial diversity, and relative abundances of specific genera were significantly different between MOM, PDHM, and formula. Additionally, our results suggest that the microbiota of MOM changes as a function of time and maternal factors. Lastly, we identified three lactotypes within MOM that have distinct microbial compositions and described the maternal factors associated with them. These findings set the stage for future research aimed at advancing our knowledge of the microbiota of preterm infant nutrition and the specific influence it may have on health outcomes.
Rocket-miR, a translational launchpad for miRNA-based antimicrobial drug development
Authors: Neff Samuel L. , Hampton Thomas H. , Koeppen Katja , Sarkar Sharanya , Latario Casey J. , Ross Benjamin D. , Stanton Bruce A. 
Published: November 2023

ABSTRACT

Developing software tools that leverage biological data sets to accelerate drug discovery is an important aspect of bioinformatic research. Here, we present a novel example: a web application called Rocket-miR that applies an existing bioinformatic algorithm (IntaRNA) to predict cross-species miRNA-mRNA interactions and identify human miRNAs with potential antimicrobial activity against antibiotic-resistant bacterial infections. Rocket-miR is the logical extension of our prior finding that human miRNA let-7b-5p impairs the ability of the ubiquitous opportunistic pathogen
Pseudomonas aeruginosa
to form biofilms and resist the bactericidal effect of β-lactam antibiotics. Rocket-miR’s point and click interface enables researchers without programming expertise to predict additional human-miRNA-pathogen interactions. Identified miRNAs can be developed into novel antimicrobials effective against the 24 clinically relevant pathogens, implicated in diseases of the lung, gut, and other organs, that are included in the application. The paper incorporates three case studies contributed by microbiologists that study human pathogens to demonstrate the usefulness and usability of the application. Rocket-miR is accessible at the following link:
http://scangeo.dartmouth.edu/RocketmiR/
.

IMPORTANCE

Antimicrobial-resistant infections contribute to millions of deaths worldwide every year. In particular, the group of bacteria collectively known as ESKAPE (
Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa,
and
Enterobacter
sp
.
) pathogens are of considerable medical concern due to their virulence and exceptional ability to develop antibiotic resistance. New kinds of antimicrobial therapies are urgently needed to treat patients for whom existing antibiotics are ineffective. The Rocket-miR application predicts targets of human miRNAs in bacterial and fungal pathogens, rapidly identifying candidate miRNA-based antimicrobials. The application’s target audience are microbiologists that have the laboratory resources to test the application’s predictions. The Rocket-miR application currently supports 24 recognized human pathogens that are relevant to numerous diseases including cystic fibrosis, chronic obstructive pulmonary disease (COPD), urinary tract infections, and pneumonia. Furthermore, the application code was designed to be easily extendible to other human pathogens that commonly cause hospital-acquired infections.
In vitro
pharmacodynamics of nemonoxacin and other antimicrobial agents against
Mycoplasma pneumoniae
Authors: Wang Na , Chen Yuancheng , Qu Xingyi , Bian Xingchen , Hu Jiali , Xu Xiaogang , Xiao Li , Liu Yang , Zhang Jing 
Published: November 2023

ABSTRACT

Mycoplasma pneumoniae
is the causative agent of respiratory infections in children and adults. Macrolide still plays a significant role in treating infections by
M. pneumoniae
. However, macrolide-resistant
M. pneumoniae
(MRMP) was encountered, causing more severe or prolonged disease worldwide from the early 2000s. Nemonoxacin is a newly developed C-8-methoxy non-fluorinated quinolone having broad-spectrum activity against gram-positive, gram-negative, and atypical pathogens
in vitro
, as well as general safety and well tolerance
in vivo
. This study aimed to assess the killing kinetics of nemonoxacin and other antimicrobial agents against MRMP and macrolide susceptible
M. pneumoniae
(MSMP) by static time-kill curves. In addition, the pharmacodynamic analyses of these drugs were determined by the sigmoid
E
max
model. The static time-kill curves indicated that nemonoxacin had good mycoplasmacidal activity against both MSMP and MRMP strains. The pharmacodynamic analysis demonstrated that the mycoplasmacidal effect of nemonoxacin was greater than those of moxifloxacin and levofloxacin based on the
K
max
, displaying a dualism of concentration dependency in low minimum inhibitory concentrations (MICs) and time dependency in high MICs. Therefore, nemonoxacin demonstrated efficacy against
M. pneumoniae in vitro
and is a potential candidate for clinical studies for assessing its therapeutic effects against
M. pneumoniae
infections. The killing pattern or PK/PD characteristics of nemonoxacin against
M. pneumoniae
from
in vitro
data, animal studies, or clinical studies merit further evaluation for treating infections caused by the organism.

IMPORTANCE

This study first reported the
in vitro
effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant
M. pneumoniae
(MRMP) and macrolide susceptible
M. pneumoniae
(MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with
M. pneumoniae
.
The
Acinetobacter baumannii
K70 and K9 capsular polysaccharides consist of related K-units linked by the same Wzy polymerase and cleaved by the same phage depolymerases
Authors: Kasimova Anastasiya A. , Sharar Nowshin S. , Ambrose Stephanie J. , Knirel Yuriy A. , Shneider Mikhail M. , Timoshina Olga Y. , Popova Anastasiya V. , Perepelov Andrey V. , Dmitrenok Andrey S. , Hsu Li Yang , Hall Ruth M. , Kenyon Johanna J. 
Published: November 2023

ABSTRACT

The extensively antibiotic-resistant
Acinetobacter baumannii
GC1(ST1
IP
) isolate SGH0807 from Singapore carries the KL70 gene cluster. The structure of the K70 capsular polysaccharide (CPS) produced by SGH0807 was determined using sugar analysis and one- and two-dimensional
1
H and
13
C NMR spectroscopy. The K70 CPS consists of branched tetrasaccharide K-units and is closely related to the previously reported K9 CPS. The KL70 and KL9 loci differ in a short segment that encodes the initiating transferase for
d
-Fuc
p
NAc in K70 and
d
-Glc
p
NAc in K9. The two structures differ only in the identity of the “first” sugar of the K-unit,
d
-Fuc
p
NAc in K70 and
d
-Glc
p
NAc in K9. This difference alters the identity of one of the sugars involved in the linkage between K-units formed by the Wzy polymerase. However, KL70 and KL9 encode an identical Wzy polymerase, designated as Wzy
KL9
, indicating that the differences between
d
-Fuc
p
NAc and
d
-Glc
p
NAc do not affect its function. Whether the difference in the first sugars was recognized by the depolymerases encoded by three K9-specific bacteriophages, AM24, BS46, and APK09, that hydrolyze the bond in K9 CPS formed by Wzy
KL9
was also examined. Purified depolymerases incubated with K70 CPS purified from SGH0807 formed oligosaccharide fragments that were monomers and dimers of the CPS cleaved at the linkage between K-units. As depolymerases encoded by phage determine host specificity by hydrolyzing specific CPS types, these phages could infect and lyse the SGH0807 K70 isolate.
A. baumannii
carrying KL70 were found in Singapore hospitals between 2006 and 2009.

IMPORTANCE

Bacteriophage show promise for the treatment of
Acinetobacter baumannii
infections that resist all therapeutically suitable antibiotics. Many tail-spike depolymerases encoded by phage that are able to degrade
A. baumannii
capsular polysaccharide (CPS) exhibit specificity for the linkage present between K-units that make up CPS polymers. This linkage is formed by a specific Wzy polymerase, and the ability to predict this linkage using sequence-based methods that identify the Wzy at the K locus could assist with the selection of phage for therapy. However, little is known about the specificity of Wzy polymerase enzymes. Here, we describe a Wzy polymerase that can accommodate two different but similar sugars as one of the residues it links and phage depolymerases that can cleave both types of bond that Wzy forms.
Nucleocapsid protein accumulates in renal tubular epithelium of a post-COVID-19 patient
Authors: Grootemaat Anita E. , Wiersma Niek , van der Niet Sanne , Schimmel Irene M. , Florquin Sandrine , Reits Eric A. , Miller Sara E. , van der Wel Nicole N. 
Published: November 2023

ABSTRACT
In this study, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins and virus particles can be detected (i) in post-mortem kidney of fatal coronavirus disease 2019 (COVID-19) patients and (ii) in renal biopsy of patients suffering from kidney failure months after combating a SARS-CoV-2 infection. Using fluorescence microscopy, antibodies against viral proteins [nucleocapsid, membrane (M), non-structural proteins (nsp) 3, 4, and 13] and double-stranded RNA (dsRNA) were validated on SARS-CoV-2-infected Vero cells. dsRNA was detected in lipid-filled electron-lucent (white) compartments in SARS-CoV-2-producing cells. In the kidney of a patient with acute kidney failure, accumulation of SARS-CoV-2 nucleocapsid N protein was detected in tubular epithelium. In contrast, none of the other viral proteins (M, nsp3, 4, 13) nor dsRNA was detected in these regions, suggesting that no viral replication takes place in the kidney of these patients. High-resolution immunoelectron microscopy demonstrated N protein accumulation in Golgi-like structures but absence of intracellular virus particles. The presence of the N protein in Golgi-like structures in kidney of patients suggests that this protein may have an unforeseen role in post-COVID-19 renal complications.

IMPORTANCE
Even though the coronavirus disease 2019 (COVID-19) pandemic is slowly developing into a conventional infectious disease, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection are still not well understood. One of the problems is that many COVID-19 cases develop acute kidney injuries. Still, it is heavily debated whether SARS-CoV-2 virus enters and actively replicates in kidney tissue and if SARS-CoV-2 virus particles can be detected in kidney during or post-infection. Here, we demonstrated that nucleocapsid N protein was detected in kidney tubular epithelium of patients that already recovered form COVID-19. The presence of the abundantly produced N protein without signs of viral replication could have implications for the recurrence of kidney disease and have a continuing effect on the immune system.
Experience and impact of gender-based violence in Honiara, Solomon Islands: a cross-sectional study recording violence over a 12-month period
Authors: Chadwick Verity , Kluckow Hannah , Mapstone Kristine , Whiffin Victoria , Ryder Bret , Rimon Mia , Hebala Hugo , Hill Sophia , Martiniuk Alexandra LC 
Published: November 2023

ObjectiveThis study aims to collect data on the experience and impact of gender-based violence experienced by women attending health clinics in Honiara, Solomon Islands.MethodAny woman over the age of 18 who attended a local health clinic in Honiara, Solomon Islands during the time of recruitment (ten consecutive weekdays in May 2015) was eligible to participate in an interviewer administered, in-person survey, gathering data on gender-based violence over the past 12 months.ResultsA total of 100 women were recruited into this study. Of these women, 47% of women reported experiencing physical or sexual violence in the past 12 months. The most common perpetrators were the woman’s husband or boyfriend. There are low rates of reporting, particularly through formal avenues such as to police or village leaders. Alcohol was involved in more than half the cases of reported violence.ConclusionWomen in this study report high rates of gender-based violence. To our knowledge, this is the only study examining women’s personal experience of gender-based violence in the Solomon Islands, with self-reported data on the frequency and nature of the violence, and the impact on women, including physical and mental, utilisation of healthcare services, police and legal involvement. Efforts to reduce gender-based violence should aim to reduce intimate partner violence, increase reporting and address wider social attitudes towards gender equality.
Inhibition and Reduction of Biofilm Production along with Their Antibiogram Pattern among Gram-Negative Clinical Isolates
Authors: Shrestha Ojaswee , Shrestha Nabina , Khanal Sadhana , Pokhrel Sushant , Maharjan Sujina , Thapa Tika Bahadur , Khanal Puspa Raj , Joshi Govardhan 
Published: November 2023

Background. Bacterial biofilm is a significant virulence factor threatening patients, leading to chronic infections and economic burdens. Therefore, it is crucial to identify biofilm production, its inhibition, and reduction. In this study, we investigated biofilm production among Gram-negative isolates and assessed the inhibitory and reduction potential of ethylene diamine tetra acetic acid (EDTA) and dimethyl sulfoxide (DMSO) towards them. In addition, we studied the antimicrobial resistance pattern of the Gram-negative isolates. Methods. Bacterial isolation and identification was done using standard microbiological techniques, following the Clinical and Laboratory Standards Institute (CLSI) guideline, 28th edition. The Kirby–Bauer disk diffusion method was used to determine the antibiotic susceptibility pattern of the isolates, and β-lactamase production was tested via the combination disk method. Biofilm formation was detected through the tissue culture plate (TCP) method. Different concentrations of EDTA and DMSO were used to determine their inhibitory and reduction properties against the biofilm. Both inhibition and reduction by the various concentrations of EDTA and DMSO were analyzed using paired t-tests. Results. Among the 110 clinical isolates, 61.8% (68) were found to be multidrug resistant (MDR). 30% (33/110) of the isolates were extended-spectrum β-lactamase (ESBL) producers, 14.5% (16/110) were metallo-β-lactamase (MBL), and 8% (9/110) were Klebsiella pneumoniae carbapenemase (KPC) producers. Biofilm formation was detected in 35.4% of the isolates. Biofilm-producing organisms showed the highest resistance to antibiotics such as cephalosporins, chloramphenicol, gentamicin, and carbapenem. The inhibition and reduction of biofilm were significantly lower (

p

< 0.05) for 1 mM of EDTA and 2% of DMSO. Conclusion. Isolates forming biofilm had a higher resistance rate and β-lactamase production compared to biofilm nonproducers. EDTA and DMSO were found to be potential antibiofilm agents. Hence, EDTA and DMSO might be an effective antibiofilm agent to control biofilm-associated infections.
Phase I/IIa Trial in Advanced Pancreatic Ductal Adenocarcinoma Treated with Cytotoxic Drug-Packaged, EGFR-Targeted Nanocells and Glycolipid-Packaged Nanocells
Authors: Ganju Vinod , Marx Gavin , Pattison Scott , Amaro-Mugridge Nancy B. , Zhao Jing-Ting , Williams Bryan R.G. , MacDiarmid Jennifer A. , Brahmbhatt Himanshu 
Published: November 2023

Abstract

Purpose:
We assessed the safety and efficacy of an EGFR-targeted, super-cytotoxic drug, PNU-159682-packaged nanocells with α-galactosyl ceramide-packaged nanocells (E-EDV-D682/GC) in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who had exhausted all treatment options.

Patients and Methods:
ENG9 was a first-in-man, single-arm, open-label, phase I/IIa, dose-escalation clinical trial. Eligible patients had advanced PDAC, Eastern Cooperative Oncology Group status 0 to 1, and failed all treatments. Primary endpoints were safety and overall survival (OS).

Results:
Of 25 enrolled patients, seven were withdrawn due to rapidly progressive disease and one patient withdrew consent. All 25 patients were assessed for toxicity, 24 patients were assessed for OS, which was also assessed for 17 patients completing one treatment cycle [evaluable subset (ES)]. Nineteen patients (76.0%) experienced at least one treatment-related adverse event (graded 1 to 2) resolving within hours. There were no safety concerns, dose reductions, patient withdrawal, or treatment-related deaths.

Median OS (mOS) was 4.4 months; however, mOS of the 17 ES patients was 6.9 months [208 days; range, 83–591 days; 95.0% confidence interval (CI), 5.6–10.3 months] and mOS of seven patients who did not complete one cycle was 1.8 months (54 days; range, 21–72; 95.0% CI, 1.2–2.2 months). Of the ES, 47.1% achieved stable disease and one partial response. Ten subjects in the ES survived over 6 months, the longest 19.7 months. During treatments, 82.0% of the ES maintained stable weight.

Conclusions:
E-EDV-D682/GC provided significant OS, minimal side effects, and weight stabilization in patients with advanced PDAC. Advanced PDAC can be safely treated with super-cytotoxic drugs via EnGeneIC Dream Vectors to overcome multidrug resistance.
‘Beyond That Which the Victim Suffers in Death Alone’
Authors: Harfouch John 
Published: November 2023

Abstract
I argue that Orientalism constructs Arabs as subjects that cannot suffer violence, particularly the violence of torture. Beginning with Edward Said’s observation that Orientalists represented ‘Arabs’ in the nineteenth-century as inorganic, metallic, and mineralized beings, I trace these themes through various sites in and around Guantanamo Bay. One finds the tropes of Orientalism in the Bybee memo as well as in the diary of Mohamedou Ould Slahi. Through these three distinct but related moments, one finds that Orientalism continues to produce Arabs as inorganic entities beyond death and thereby immune to violence. Insofar as imperialism has co-opted the language of non-violence by constructing its enemies as inviolable, one must recognize the Orientalized Arab as a receptor of limitless ‘non-violent’ hostilities.
gdpr as an Instance of Neoliberal Governmentality: a Critical Analysis of the Current ‘Gold Standard’ of Data Protection
Authors: Manokha Ivan 
Published: November 2023

Abstract
The gdpr today is commonly seen as a ‘gold standard’ of personal data regulation. While recognizing the importance of the gdpr, especially in affirming that personal data belongs to the individuals rather than commercial or public entities, this paper seeks to demonstrate that such a view is, nevertheless, problematic: first, what the gdpr, along with similar regulations inspired by it elsewhere, effectively does is help organise the functioning of the personal data market in which private user data continues to be commodified and used to generate massive profits by various firms and platforms; second, the gdpr does it in a paradigmatically neoliberal manner – public authorities create a legal framework for a market, and devolve the responsibility for managing negative consequences to the affected populations themselves, presenting it as their ‘empowerment’; third, just as it is often the case with neoliberal governmentality in other sectors, the tool provided by the gdpr to individuals to protect themselves – here the right to reject the terms of service (tos) of different providers – embodies and reproduces an asymmetric power relation between capital and society – here between service providers and users – and effectively ensures that individuals continue to acquiesce to the collection and commodification of their private data: on the one hand, the complexity of different tos, their ‘take-it-or-leave-it’ nature, length, etc., render the evaluation of privacy implications very difficult for individual users; second, in some cases, the rejection of tos is impossible because access to the service in question is indispensable, as in the case of platform workers. Users mechanically click ‘Accept’ which is seen as an instance of ‘informed consent,’ and which in turn makes the collection and monetization of personal data legal.