bluuebunny/crossref_metadata_2025 huggingface dataset:
Did College Students Suffer Stress During the Covid-19 Lockdown?
Authors: Valentín Alberto , López Pérez Estrella , González-Tablas Sastre Mª del Mar , Mateos García Pedro M. , Gordillo León Fernando
Published: February 2025

Lockdown involves social isolation that can have a negative impact at the psychological level, which is why several studies have analyzed the relationship between confinement and possible emotional disorders or alterations. This study aims to analyze the symptoms of posttraumatic stress disorder (PTSD) pertaining to stressors that could appear during the confinement of college students, in addition to their evolution and the differential effects that contagion might cause to these symptoms. 270 students responded to a survey created specifically for this study. The survey was administered once a week during the last four weeks of confinement. The students' responses did not show evidence of PTSD symptoms. Furthermore, the low frequency and intensity of symptoms decreases as the weeks of confinement progress. Likewise, infected students show more symptoms than non-infected students, except in respect of the stressor Fear of contagion. The confinement experienced by our students has not been a source of stress. Although this may seem positive, it also promotes risky behaviors, so it should be considered important to carry out awareness campaigns in order to promote habits that help prevent the transmission of the virus.
Analysis of Pull-in Parameters of a micro electro mechanical Beam with van der Waals force using Modified couple stress theory
Authors: Saw Gyana Ranjan , Singh Suraj , Chakraborty Goutam
Published: February 2025

This study investigates the pull-in parameters of a microcantilever beam influenced by electrostatic and van der Waals forces in MEMS devices. The classical continuum theory(CCMT) is inadequate because of the presence of nonpolar molecules, voids, and dielectric materials at the micro or nanoscale. Modified couple stress theory(MCST) is a nonclassical continuum technique used in microbeams for evolution of the length scale parameter(lm). Non-linearity due to large scale deflection and van der Waals force is highly significant at the micro scale. The Galerkin method is used to solve the governing equation of microbeam model. The comparison of eigenfrequencies is conducted by numerical, finite element based method while varying the mass of microplate. The pull-in phenomena occurs when the actuating force is exceeds the mechanical force. The static pull-in parameters are determined using on CCMT, and Meshless local petrov galerkin(MLPG) methods and verified through COMSOL software. The pull-in voltage(Vpi), displacement(wpi), van der Waals parameter(Cpi) are in close match with numerical and analytical methods. The variation lm is influenced by damping constant, stiffness of microbeam under dynamic pull-in conditions.
RNF20 dual regulation of MDA5 signaling to maintain immune homeostasis in chickens
Authors: Wang Jie , Liu Qiuju , Zhang Kehui , Zhao Shurui , Shao Qi , Fu Feiyu , Ma Jingjiao , Wang Zhaofei , Yan Ya-xian , Wang Hengan , Sun Jianhe , Cheng Yuqiang
Published: February 2025

RIG-I and MDA5, known as the RIG-I-like receptors (RLRs), play a pivotal role in inducing antiviral responses to RNA viral infections. While chickens lack RIG-I, they possess a functionally enhanced MDA5 that recognizes pathogens and regulates immunity, underscoring the critical role of MDA5 in maintaining immune homeostasis in chickens. However, the precise mechanisms governing the expression and optimal activation of MDA5 remain unclear. Here, we reveal that the chicken E3 ubiquitin ligase RNF20 is essential for modulating MDA5-mediated innate immune homeostasis. Transcriptome sequencing analysis revealed that RNA viral infection of DF-1 cells significantly upregulated the expression of chicken RNF20. Overexpression of RNF20 markedly suppresses the expression of chicken innate immunity-related genes, while RNF20 knockout leads to immune deficiency both
in vivo
and
in vitro
. Mechanistically, RNF20 is located in the nucleus, where it maintains the basic expression and regulates the inducible expression of MDA5 to establish immune defense during the early infection phase. In the late phase, RNF20 translocates to the cytoplasm, where it facilitates the K27- and K48-linked polyubiquitination and subsequent degradation of MDA5, thereby preventing immune overstimulation. Overall, this study establishes RNF20 as an important E3 ubiquitin ligase that maintains chicken innate immune homeostasis.

IMPORTANCE

Chicken MDA5 is an important RNA viral sensor for initiating the antiviral innate immune response. The protein level of MDA5 must be tightly regulated to maintain antiviral innate immune homeostasis. In this study, we demonstrate that the E3 ubiquitin ligase RNF20 precisely regulates MDA5 protein stabilization through nucleoplasmic translocation. Specifically, in uninfected and during early infection, RNF20 regulates MDA5 transcription in the nucleus. While in the late stages of infection, RNF20 translocates out of the nucleus and catalyzes the ubiquitinated degradation of MDA5. Thus, RNF20 is important in regulating chicken antiviral innate immune homeostasis.
Deployment of a
Vibrio cholerae
ordered transposon mutant library in a quorum-competent genetic background
Authors: Grant Nkrumah A. , Donkor Gracious Yoofi , Sontz Jordan , Soto William , Waters Christopher M.
Published: February 2025

Vibrio cholerae
, the causative agent of cholera, has sparked seven pandemics in recent centuries, with the current one being the most prolonged.
V. cholerae’s
pathogenesis hinges on its ability to switch between low- and high-cell-density gene regulatory states, enabling transmission between the host and the environment. Previously, a transposon mutant library for
V. cholerae
was created to support investigations aimed toward uncovering the genetic determinants of its pathogenesis. However, subsequent sequencing uncovered a mutation in the gene
luxO
of the parent strain, rendering mutants unable to exhibit high-cell-density behaviors. In this study, we used chitin-independent natural transformation to move transposon insertions from these low-cell-density mutants into a wild-type genomic background. Library transfer was aided by a novel gDNA extraction method we developed using thymol, which also showed high lysis specificity for
Vibrio
. The resulting Grant Library comprises 3,102 unique transposon mutants, covering 79.8% of
V. cholerae’s
open reading frames. Whole-genome sequencing of randomly selected mutants demonstrates 100% precision in transposon transfer to cognate genomic positions of the recipient strain in every strain analyzed. Notably, in no instance did the
luxO
mutation transfer into the wild-type background. Our research uncovered density-dependent epistasis in growth on inosine, an immunomodulatory metabolite secreted by gut bacteria that is implicated in enhancing gut barrier functions. Additionally, Grant Library mutants retain the plasmid that enables rapid, scarless genomic editing. In summary, the Grant Library reintroduces organismal-relevant genetic contexts absent in the low-cell-density-locked library equivalent.

Ordered transposon mutant libraries are essential tools for catalyzing research by providing access to null mutants of all non-essential genes. Such a library was previously generated for
Vibrio cholerae
, but whole-genome sequencing revealed that this library was made using a parent strain that is unable to exhibit cell-cell communication known as quorum sensing. Here, we utilize natural competence combined with a novel, high-throughput genomic DNA extraction method to regenerate the signaling incompetent
V. cholerae
ordered transposon mutant library in quorum-sensing-competent strain. Our library provides researchers with a powerful tool to understand
V. cholerae
biology within a genetic context that influences how it transitions from an environmentally benign organism to a disease-causing pathogen.
Dual function of
Candida auris
mannosyltransferase, MTN5, in biofilm community protection from antifungal therapy and the host
Authors: Zarnowski Robert , Horton Mark V. , Johnson Chad J. , Vang Por Choua , Uram Jeremy , Fernando Liyanage Devthilini Pasasum , Vlach Jiri , Heiss Christian , Azadi Parastoo , Nett Jeniel E. , Andes David R.
Published: February 2025

Screen of mutants from a mannosyltransferase family identified the importance of
MNT5
for
C. auris
biofilm drug resistance and neutrophil evasion. Biochemical analysis of the
mnt5∆
mutant matrix and cell wall identified alterations in the mannan structures. Resistance and matrix for
mnt5∆
were restored with delivery of wild-type matrix via extracellular vesicles. Analysis of the
mnt5
∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for
MNT5
in mannan masking of pathogen-associated molecular patterns.

IMPORTANCE

C. auris
recalcitrance is linked to biofilm drug resistance and immune evasion. The mannosyltransferase encoded by
MNT5
is necessary for both phenotypes and may serve as a useful therapeutic target.
A
Ralstonia solanacearum
effector regulates plant cell death by disrupting the homeostasis of the BPA1-ACD11 complex
Authors: Xue Bingbing , Zhou Yan , Xie Yongxiao , Huang Xiaocheng , Zhang Jinye , Zhang Yang , Zhong Wenyan , Zhao Jinjia , Zheng Dehong , Ruan Lifang
Published: February 2025

Effectors secreted by phytopathogenic bacteria can suppress ETI responses induced by avirulence effectors, thereby overcoming crop resistance. However, the detailed mechanisms remain largely unknown. We report that the effector RipD from
Ralstonia solanacearum
regulates plant cell death in a protein abundance-dependent manner. RipD targets
Arabidopsis
BPA1, which directly interacts with the key cell death negative regulator ACD11. RipD competes with ACD11 for binding to BPA1, leading to the selective degradation of BPA1 via autophagy, sparing ACD11. A lower dose of RipD promotes BPA1 degradation but leads to ACD11 accumulation, thereby inhibiting RipAA-induced cell death. Conversely, higher levels of RipD degrade both BPA1 and ACD11, resulting in autophagy-dependent cell death. Visualization of RipD delivery by
R. solanacearum
indicated that it reaches levels sufficient to promote ACD11 accumulation and inhibit cell death. Our study reveals a novel mechanism by which an effector inhibits ETI and, for the first time, highlights the critical role of protein abundance in its function.

IMPORTANCE

R. solanacearum
infects major economic crops, notably tomato, potato, and tobacco, leading to substantial yield reductions and economic losses. This pathogen utilizes various type III effectors to suppress host resistance, often resulting in weakened or lost resistance. However, the underlying mechanisms remain largely unknown. Here, we reveal a novel mechanism by which RipD targets the BPA1-ACD11 complex, which is involved in host immunity and cell death. RipD regulates ACD11 protein homeostasis in a dose-dependent manner by competitively binding and activating autophagy, thereby modulating plant cell death. Importantly, visualization analysis revealed that the amount of RipD secreted by
R. solanacearum
into host cells is sufficient to inhibit Avr effector-induced cell death. Our study highlights for the first time the critical role of effector dosage, deepening the understanding of how
R. solanacearum
suppresses host ETI-related cell death and providing guidance and resources for breeding bacterial wilt resistance.
A novel plasmid-encoded transposon-derived small RNA reveals the mechanism of sRNA-regulated bacterial persistence
Authors: Lin Shu-Ling , Nie Qi-Chang , Law Carmen Oi-Kwan , Pham Hoa-Quynh , Chau Ho-Fai , Lau Terrence Chi-Kong
Published: February 2025

Small regulatory RNAs (sRNAs) in bacteria are crucial for controlling various cellular functions and provide immediate response to the environmental stresses. Antibiotic persistence is a phenomenon that a small subpopulation of bacteria survives under the exposure of a lethal concentration of antibiotics, potentially leading to the development of drug resistance in bacteria. Here, we reported a novel transposon-derived sRNA called stnpA, which can modulate fosfomycin persistence of the bacteria. The stnpA sRNA located in the transposon with its own promoter is highly conserved among the prevalent multidrug resistance (MDR) plasmids in various pathogenic bacteria and expressed in response to the fosfomycin stress. It can directly bind to the ABC transporter, YadG, whereas this protein–RNA interaction modulated the export of fosfomycin and led to the enhancement of bacterial persistence. According to our knowledge, stnpA is the first identified transposon-derived sRNA, which controlled antibiotic persistence of bacteria, and our work demonstrated that nonresistance genes on MDR plasmids such as plasmid-encoded sRNA can provide additional survival advantages to the bacterial host against the antibiotics. In addition, the stnpA sRNA can be potentially utilized as the druggable target for the development of novel therapeutic strategies to overcome bacterial persistence.

IMPORTANCE

This study unveils a groundbreaking discovery in the realm of bacterial antibiotic persistence, highlighting the pivotal role of a newly identified small RNA (sRNA) called stnpA, which is a multidrug resistance plasmid-encoded transposon-derived sRNA that interacts directly with ABC transporter YadG to modulate the efflux of fosfomycin. Our findings elucidate a novel mechanism of small RNA-regulated fosfomycin persistence in bacteria that provides the potential pathway for the emergence of drug resistance in bacteria upon antibiotic treatment. Importantly, this study provides the first example of linking sRNA regulation to antibiotic persistence, presenting stnpA sRNA as a potential therapeutic target. This study underscores the critical role of noncoding RNAs in bacterial adaptation and offers valuable insights for developing new strategies to combat antibiotic persistence.
Nutrition-induced changes in the microbiota can cause dysbiosis and disease development
Authors: Lachnit Tim , Ulrich Laura , Willmer Fiete M. , Hasenbein Tim , Steiner Leon X. , Wolters Maria , Herbst Eva M. , Deines Peter
Published: February 2025

Eukaryotic organisms are associated with complex microbial communities. Changes within these communities have been implicated in disease development. Nonetheless, it remains unclear whether these changes are a cause or a consequence of disease. Here, we report a causal link between environment-induced shifts in the microbiota and disease development. Using the model organism
Hydra
, we observed changes in microbial composition when transferring laboratory-grown
Hydra
to natural lake environments. These shifts were caused not only by new colonizers, through the process of community coalescence (merging of previously separate microbial communities), but also by lake water nutrients. Moreover, selective manipulation of the nutrient environment induced compound-specific shifts in the microbiota followed by disease development. Finally, L-arginine supplementation alone caused a transition in
Pseudomonas
from symbiotic to pathogenic, leading to an upregulation of immune response genes, tissue degradation, and host death. These findings challenge the notion that the host-associated microbiota is exclusively controlled by the host, highlighting the dynamic interplay between host epithelial environment, microbial colonizer pool, and nutrient conditions of the surrounding water. Furthermore, our results show that overfeeding of the microbiota allows for uncontrolled microbial growth and versatile interactions with the host. Environmental conditions may thus render symbionts a potential hazard to their hosts, blurring the divide between pathogenic and non-pathogenic microbes.

IMPORTANCE

This study highlights the critical need to understand the dynamic interplay between host-associated microbiota and environmental factors to obtain a holistic view on organismal health. Our results demonstrate that ecosystem-wide microbial trafficking (community coalescence) and environmental nutrient conditions reshape microbial communities with profound implications for host health. By exploring nutrient-driven changes in microbial composition, our research finds experimental support for the “overfeeding hypothesis,” which states that overfeeding alters the functionality of the host microbiota such that an overabundance in nutrients can facilitate disease development, transforming non-pathogenic microbes into pathogens. These findings emphasize the critical role of metabolic interactions driving microbial pathogenicity. Furthermore, our research provides empirical evidence for the “pathogenic potential” concept, challenging traditional distinctions between pathogenic and non-pathogenic microbes and supporting the idea that any microbe can become pathogenic under certain conditions.
Comparative metagenomic analysis of 16S RNA amplicon sequencing of bacterial population of an industrial site contaminated with halogenated anilines
Authors: Tobun Olukemi Ajibola , Adebusoye Sunday Adekunle , Ilori Matthew Olusoji
Published: February 2025

Here, we use 16S rRNA gene sequencing to identify bacterial communities in three soil samples from contaminated soils with halogenated anilines and empty soil (serving as control) in Lagos state, Nigeria. BNE, BLB, and BLC had unique operational taxonomic units (OTUs) of 160, 1,797, and 4,815, respectively. Proteobacteria were the dominant phyla across all samples.
Microbiome diversity in soils of the agro-ecological zones of Bangladesh
Authors: Islam Nurul , Hoque M. Nazmul , Hossen Sabbir , Gilman Abu Ahsan , Islam Tofazzal
Published: February 2025

Diversity and composition of soil bacteriome across various agro-ecological zones (AEZs) in Bangladesh were unveiled using 16S rRNA gene sequencing. The mapping of bacterial communities in each AEZ has laid a foundation for detailed mapping and engineering of soil microbiome in deltaic Bangladesh soils for mitigating impact of climate change and promoting sustainable agriculture.
Complete genome sequences of
Sellimonas intestinalis
JCM 30749
T
,
Sellimonas caecigallum
JCM 35759
T
, and
Sellimonas catena
JCM 35622
T
and JCM 35623
Authors: Koike Kazuyoshi , Murotomi Kazutoshi , Hamajima Mayu , Tourlousse Dieter M. , Hisatomi Atsushi , Sakamoto Mitsuo , Sekiguchi Yuji
Published: February 2025

We obtained complete genome sequences of
Sellimonas intestinalis
JCM 30749
T
, “
Sellimonas caecigallum
” JCM 35759
T
,
Sellimonas catena
JCM 35622
T
, and
Sellimonas catena
JCM 35623. All four genomes consist of a single circular chromosome, with lengths of 2,758,996 to 3,825,976 base pairs and G + C contents of 45.12% to 45.59%.
BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of
Mycoplasma pneumoniae
pneumonia in children
Authors: Jin Yun-Yun , Guo Yun , Xiong Su-Wan , Zhang Na , Chen Jian-Huan , Liu Feng
Published: February 2025

Mycoplasma pneumoniae
is an important human respiratory pathogen that causes mild-to-moderate community-acquired
M. pneumoniae
pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it could be involved in the epigenetic regulation of host response to
M. pneumoniae
infection. In the present study, we performed an epitranscriptomic analysis of adenosine to inosine (A-to-I) editing in 39 bronchoalveolar lavage fluid (BALF) samples from the severe side (SS) and the opposite side (OS) of patients with MPP. Our editome profiling identified 87 differential RNA editing (DRE) events in 50 genes, especially missense editing events that recoded C-C motif chemokine receptor-like 2 (
CCRL2
, p.K147R) and cyclin I (
CCNI
, p.R75G). The expression of adenosine deaminase acting on RNA (
ADAR
) significantly increased on SS compared to OS and positively correlated with the average RNA editing level and individual DRE events. Meanwhile, functional enrichment analysis showed that DRE was observed in genes primarily associated with the negative regulation of innate immune response, type I interferon production, and cytokine production. Further comparison of SS between complicated MPP (CMPP) and non-complicated MPP (NCMPP) revealed RNA editing events associated with MPP complications, with a higher
ADAR
expression in CMPP than NCMPP. By identifying DRE events as biomarkers associated with MPP severity and complications, our editome profiling provides new insight into the potential role played by A-to-I RNA editing in modulating the host’s immune system during
M. pneumoniae
infection.

IMPORTANCE

Our research investigates how
Mycoplasma pneumoniae
, a common respiratory pathogen, influences how our cells modify their genetic instructions. By studying RNA editing changes in bronchoalveolar lavage fluid from patients with
M. pneumoniae
pneumonia, we aim to investigate how
M. pneumoniae
infection alters epigenetics and contributes to the disease severity and complications. Understanding such epigenetic alterations not only sheds light on the mechanisms underlying
M. pneumoniae
infection but also holds potential implications for developing better diagnostic tools and therapies. Ultimately, this work may facilitate the design of more targeted treatments to alleviate the impact of respiratory infections caused by the pathogen. Our findings may also offer broader insights into how microbial infections reshape immune processes, highlighting the importance of RNA editing in host-pathogen interactions.
Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
Authors: Woh Pei Yee , Chen Yehao , Kumpitsch Christina , Mohammadzadeh Rokhsareh , Schmidt Laura , Moissl-Eichinger Christine
Published: February 2025

The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically
Methanobrevibacter
species. Most MS patients were female (80/115), aged 25–72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (
n
= 21), fingolimod (
n
= 20), glatiramer acetate (
n
= 14), interferon (
n
= 18), natalizumab (
n
= 6), or ocrelizumab/rituximab (
n
= 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of
Methanobrevibacter smithii
and
M.
sp900766745 compared to untreated patients. Notably,
M.
sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for
M. smithii
and
M.
sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.

IMPORTANCE

Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20–30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome’s impact on MS and improving patient management.
Fur-regulated urease contributes to the environmental adaptation of
Yersinia pseudotuberculosis
Authors: Wang Junyang , Fu Peishuai , He Xinquan , Liu Yuqi , Zuo Yuxin , Wei Zhiyan , Wang Yao , Yang Yantao , Li Changfu , Shen Xihui , Zhu Lingfang
Published: February 2025

Urease converts urea into ammonia and carbon dioxide, providing a nitrogen and carbon source for microbial growth and serving as an important mechanism for human bacterial pathogens to survive in acidic conditions, which can be regulated by many factors. As a global regulator, the ferric uptake regulator (Fur) regulates a series of genes and pathways involved in many different cellular processes and the virulence of the enteric bacterium
Yersinia pseudotuberculosis
(
Yptb
). However, whether Fur regulates the urease activity in
Yptb
was still unknown. In this study, we found that urease is positively regulated by Fur in response to manganese ions (Mn
2+
), and this regulation by Fur is mediated by specific recognition of the promoter region of urease in
Yptb
. Furthermore, urease is induced by Mn
2+
via Fur under low nutrient conditions. Moreover, we provided evidence that urease plays an important role in acid and osmotic stress resistance, biofilm formation, and virulence of
Yptb
. Our findings provide insights into understanding the regulatory mechanism and multiple functions of urease in
Yptb
.

IMPORTANCE

Urease catalyzes the breakdown of urea into ammonia and carbamate, which are widely distributed among bacterial species and play an important role as an important acid resistance system and virulence factor. In most bacterial species, urease expression is tightly regulated in response to environmental cues such as nitrogen status, pH, growth phase, substrate availability, or transcriptional regulators. In this study, we found that urease from
Yptb
is positively regulated by Fur in response to Mn
2+
under low nutrient conditions, which functions to combat acid and osmotic stress and enhance biofilm formation, and plays a crucial role in virulence. Importantly, this is the first demonstration of a direct role for Fur and Mn
2+
in regulating urease expression in
Yptb
. This study provides a comprehensive understanding of the regulatory mechanisms and functions of urease from
Yptb
.
Male ductal carcinomain situ(DCIS) at a young age
Authors: Vastmans Emma , Han Sileny , Floris Giuseppe , Neven Patrick
Published: February 2025

In this case, a man in his late 20s visited his general practitioner with unilateral left nipple discharge. Initially, he was treated with antibiotics and the nipple discharge stopped. When the discharge recurred after a few weeks, the patient was referred to the multidisciplinary breast centre in UZ Leuven. Clinical examination revealed an otherwise healthy but obese man (body mass index of 31 kg/m²). On examination, we were able to evacuate bloody discharge from a single duct by mild compression of the left nipple.

The bilateral mammography and ultrasound showed an irregular retroareolar density of 40×50 mm with adjacent, multiple clustered microcalcifications over a total distance of 20 mm on the left side.

The histopathological report after core needle biopsy revealed a poorly differentiated ductal carcinomain situ. Genetic testing for hereditary breast–ovarian cancer genes was negative. A simple left mastectomy with sentinel lymph node biopsy was performed. There was no indication for adjuvant chemotherapy or radiotherapy, nor for adjuvant endocrine therapy.
Visceral leishmaniasis mimicking inflammatory myositis that led to haemophagocytic lymphohistiocytosis
Authors: Ibad Illiasul K , Vankayala Akshay , Manwatkar Abhilasha , Mathew John
Published: February 2025

Idiopathic inflammatory myositis (IIM) is a heterogeneous group of immune-mediated diseases that mainly affect the skeletal muscles and skin. This case report narrates the story of a middle-aged man who presented with fever, weight loss, muscle weakness and skin rash and was treated elsewhere for probable dermatomyositis with steroids, methotrexate and rituximab. He presented to our facility with persistent fever and hyperpigmented skin rash. Detailed re-evaluation ultimately led to the final diagnosis of haemophagocytic lymphohistiocytosis due to visceral leishmaniasis. He was treated with liposomal amphotericin B. The patient responded well to treatment and did not require further immunosuppression during follow-up. This case highlights the importance of carefully recognising atypical findings to differentiate the IIM from its mimics, particularly infections in endemic areas.
Aplastic anaemia, pernicious anaemia and autoimmune thyroiditis following an episode of EBV-associated hepatitis
Authors: Gunchenko Melissa , Shapiro Chandler , Jain Shivi , Doozandeh Hamideh
Published: February 2025

Epstein-Barr virus (EBV) affects over 90% of the global population and has been linked to several autoimmune disorders. This report describes a patient with EBV-associated hepatitis who subsequently developed aplastic anaemia, pernicious anaemia and autoimmune thyroiditis. The patient was treated with an immunosuppressive regimen with gradual improvement in his pancytopenia and autoimmune thyroiditis. This report highlights the importance of a comprehensive evaluation and close monitoring of patients presenting with acute or recent EBV infection. Clinicians are urged to recognise autoimmune sequelae, as early intervention can be life-saving.
Timely intervention of spontaneous scleral melt in Marfan syndrome
Authors: Mishra Nibha , Priya Priyanshi , Yadav Niraj Kumar , Kaur Apjit
Published: February 2025

A young man in his late adolescence presented with a gradually progressive diminution of vision in both eyes for 3 years. A general physical examination revealed features suggestive of Marfan syndrome, with a positive family history. Ocular examination revealed a superonasal lens subluxation with a myopic fundus in both eyes. The patient underwent pars plana lensectomy with anterior vitrectomy in the right eye followed by the left eye. The right eye surgery was uneventful, and the patient was left aphakic. On the first postoperative day, the left eye developed hypotony. By the second day, spontaneous scleral melt was noted posterior to the surgical wound with severe hypotony and loss of globe architecture. The patient was taken up for emergency surgery with an amniotic membrane graft over the area of scleral melt and was started on oral ciclosporin (100 mg). Postoperatively, the patient’s globe stabilised. After 1 week, the patient’s vision increased to 6/24 with normal intraocular pressure.
Clinical phenotyping of people living with type 1 diabetes according to their levels of diabetes-related distress: results from the SFDT1 cohort
Authors: Canha Dulce , Aguayo Gloria , Cosson Emmanuel , Vaduva Patricia , Renard Eric , Alzaid Fawaz , Bonnet Fabrice , Hadjadj Samy , Potier Louis , Vergès Bruno , Lablanche Sandrine , Benhamou Pierre Yves , Hanaire Helene , Reznik Yves , Riveline Jean-Pierre , Fagherazzi Guy
Published: February 2025

Introduction

Type 1 diabetes is burdensome, requiring complex daily management and making people more prone to emotional distress. To better detect diabetes-related distress (DD) and identify at-risk patients, we aimed to provide an in-depth characterization of DD in people with type 1 diabetes.

Research design and methods

We included adults with type 1 diabetes from theSuivi en France des personnes avec un Diabète de Type 1cohort who filled in the Problem Areas in Diabetes questionnaire (PAID ≥40 indicates high DD). Age and sex-adjusted multivariable logistic regression models analyzed individual characteristics, clinical indicators, diabetes-related complications and psychological factors. We further analyzed DD according to six data-driven subdimensions: emotional distress, fear of complications, social distress, eating distress, management distress, and diabetes burnout.

Results

In total, 1220 participants (50.6% female, age 42 years (SD 13.9), diabetes duration 24.7 years (13.6)) had a total mean PAID score of 39.6 (21.7) and 592 (48.5%) reported high DD. Leading subdimensions of DD included fear of complications (50.1 (24.4)) and diabetes burnout (45.9 (24.5)). Females, younger age, social vulnerability, smoking, and the presence of retinopathy were positively associated with high DD (p<0.05). We observed similar DD levels across HbA1c levels and treatment modalities, including automated insulin delivery and continuous glucose monitoring use. Several psychological factors, such as anxiety/depression, poor sleep quality, and treatment burden, were strongly associated with DD (p<0.001).

Conclusions

We provide a holistic clinical phenotyping approach that enables the identification of determinants and prevalence of DD, overall and according to key DD subdimensions, in a large and diverse population. Our results underscore the importance of developing DD-targeted prevention and intervention strategies focused specifically on high-risk groups and the most impactful distress subdimensions to reduce the impact of type 1 diabetes burden.

Trial registration number

NCT04657783.
Intravenous lidocaine for gut function recovery in colonic surgery: a health economic evaluation of the ALLEGRO randomised clinical trial
Authors: Atter Marek , Stoddart Andrew , Cotton Seonaidh , Vadiveloo Thenmalar , Innes Karen , Balfour Angie , Arnott Robert , Aucott Lorna , Batham Zoe , Foo Irwin , MacLennan Graeme , Nimmo Susan , Speake Doug , Norrie John , Paterson Hugh
Published: February 2025

Objectives

To compare costs, health outcomes and cost-effectiveness of using intravenous lidocaine (bolus given at induction of anaesthesia, followed by infusion for 6–12 hours) during colorectal surgery to improve the return of gastrointestinal function.

Design

Within-trial planned analysis of data from a randomised controlled trial using an intention-to-treat approach.

Setting

27 hospitals from across the UK.

Participants

557 patients aged 25–91 having minimally invasive elective colorectal resection.

Intervention

A 1:1 randomisation between intravenous lidocaine and placebo, minimised for age (<50 years, 50–74 years, ≥75 years), gender, and trial centre.

Primary outcome measures

Mean differences between trial arms in 30-day and 90-day quality-adjusted life-years (QALYs) and 30-day total National Health Service costs, as well as the 30-day incremental cost-effectiveness ratio.

Results

Compliance and data quality were high. Intravenous lidocaine is associated with differences of £38 (95% CI: −£463, £589) in total 30-day costs, −0.0005 (95% CI: −0.0027, 0.0015) in 30-day QALYs and −0.0008 (95% CI: −0.0066, 0.0048) in 90-day QALYs. No large, statistically significant or meaningful differences in primary or secondary outcome measures between trial arms were detected, other than for the intervention costs.

Conclusion

Intravenous lidocaine is not found to impact costs or health outcomes for patients undergoing colorectal surgery. In the absence of a clinical effect, disinvestment from perioperative lidocaine could save costs associated with infusion monitoring.

Trial registration number

International Standard Randomised Controlled Trial Number 52352431.
Updates on vascular dementia
Authors: Ng Sabrina , Hornblass Ava , Habibi Parnian , Ikramuddin Salman , Chen Jeffrey , Feng Wayne , Cai Dongming
Published: February 2025

Vascular dementia (VaD) is the second leading cause of dementia after Alzheimer’s disease (AD). In comparison to AD, there is a decline in the incidence of VaD due to recent improvements in cardiovascular risk factors. Brain hypoperfusion and hypoxia due to vascular pathologies have been postulated as the primary disease mechanism of VaD. However, other factors such as neuroinflammation may also contribute to the development of VaD. Non-modifiable and modifiable risk factors have been attributed to VaD. The clinical features overlapping between AD and VaD create significant challenges for physicians. Newly developed biomarkers may potentially help differentiate VaD from other forms of dementia. Unlike AD, there is no Food and Drug Administration-approved drug or device for treating VaD. Current treatment options mainly target symptoms rather than slowing the development or progression of VaD. There are ongoing research studies testing the efficacy of various therapeutic strategies for VaD. In this narrative review, we will summarise current findings on epidemiology, attributed risk factors and disease mechanisms, as well as emphasise the importance of optimising lifestyle modifications and comorbid condition management in preventing or slowing down the development of VaD. Finally, current therapies and ongoing research studies of novel therapeutic interventions such as stem-cell therapy and neuromodulation are highlighted.
Development and Evaluation of a Sensitive Approach for Detection and Recovery of Third-generation Cephalosporin- and Carbapenem-resistant Enterobacterales from Ready-to-Eat Frozen Stone Fruit
Authors: Nasta Adeeb , Cooper Ashley L. , Tackabury Irelynd Victoria , Anastasiadis Chloe , Lau Calvin , Brown Liam , Smith Myron L. , Tamber Sandeep , Carrillo Catherine D.
Published: February 2025

Antimicrobial resistance (AMR) is a global public health threat, but the role of foods in its dissemination is poorly understood. We examined the incidence of foodborne bacteria carrying AMR genes considered high-priority research targets by the World Health Organization. Frozen, ready-to-eat, avocado, coconut, mango, and peach (n=161) were tested for bacteria encoding extended-spectrum β-lactamases (ESBLs) and carbapenemases. Over 600 presumptive-positive isolates were recovered and analyzed with a pooled sequencing strategy (Pool-seq). Coconut samples exhibited the highest bacterial loads and prevalence/diversity of AMR genes. Isolates harbouring the β-lactamase genes blaCTX-M, blaTEM, and blaSHV, identified in 14 coconut and two mango samples, were further characterized by whole-genome sequencing and antimicrobial susceptibility testing. The most common gene was blaCTX-M-15, detected in 20 unique strains. Two carbapenemase-producing strains were isolated from coconut: Enterobacter roggenkampii encoding blaNDM-1 and Escherichia coli encoding blaNDM-5. Subsequent qPCR analysis of enrichments for blaCTX-M/blaNDM indicated a potentially higher prevalence of these genes than observed by colony screening. This study presents a practical method for recovering ESBL- and carbapenemase-producing bacteria from foods. Mapping their distribution in food products is crucial to assessing the role of foods in the global spread of AMR and developing effective public health interventions.
Measurement of K fluorescence analysis in ancient bone using X-ray transition edge sensor and semiconductor detectors
Authors: Li Zhi-Wei , Guo Si-Ming , Zhang Shuo , Wu Jin-Jie , Wang Zhen , Li Nan , Wang Zhong-Tao
Published: February 2025

Transition edge sensor (TES) have high energy resolution, which can extremely improve in various scientific experiments the energy spectrum analysis capability and have a wide range of applications in almost all fields covering the whole wave band of electromagnetic waves. The same Chinese ancient human bone sample was measured by fluorescence analysis using SDD, Si-PIN detector and TES detector. Typical representative results among the measurements of the three detectors were selected for comparative analyses. The experimental results showed that the TES detector has obvious advantages compared with the semiconductor detector, with a resolution of 21.2eV@3.69 keV, compared to 115.8 eV @ 3.69 keV and 143.9 eV @ 3.69 for SDD and Si-PIN detectors, respectively. TES detector even found some spectral lines that cannot be measured by semiconductor detectors, such as the 0.916 keV L line of Cu, L line of 2.86 keV Rh and so on. The experimental results demonstrate the TES detector’s outstanding performance in elemental spectral line detection. Compared to observations with semiconductor detectors, using X-ray TES enables clear resolution of spectral lines corresponding to elements present in the sample.
Solar-Triggered Engineered Fe Doped ZnS Nanoparticles for Environmental Remediation
Authors: Javaid Nisar , Ullah Asad , Rafiq Asma , Asghar Muzammal , Akbar Zubair , Naz Misbah , Samreen Ayesha , Riaz Saira , Naseem S
Published: February 2025

Modern society requires cutting-edge technologies built on renewable and sustainable energy sources to address the problems of environmental purification. In the present study, synthesis of pure and iron (Fe) doped zinc sulfide (ZnS) nanoparticles were carried out using co-precipitation technique. The prepared samples were characterized by x-ray diffraction (XRD) analysis, UV–visible spectroscopy, fourier transform infrared spectroscopy (FTIR), and photoluminescence spectroscopy (PL), to reveal the alterations in the structure and morphology of nanomaterials. XRD analysis showed the wurtzite phase of prepared nanoparticles. UV–visible spectroscopy reveals intensive absorption in the visible region upon Fe doping. The inclusion of Fe dopants into ZnS led to a decrease in the bandgap energy. FTIR spectra confirmed the presence of specific functional groups linked to the vibrational modes of samples. PL spectroscopy was used to study the transfer behavior of photo-generated electrons and holes in as prepared samples. The photoactivity and kinetics of photo-products were explored by monitoring photo-decolorization of methylene blue (MB) under solar irradiation. Photodecomposition of MB was dramatically increased when Fe-doped samples were employed relative to pristine ZnS. The present study suggests that Fe doped ZnS nanoparticles may be used as an efficient photocatalyst in wastewater treatment and associated environmental applications.
Supplementary figure 2 from Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaew Intawat , Delgado-Calle Jesus
Published: February 2025

Supplementary figure 2
Phase 1 trial of selinexor in pediatric recurrent/refractory solid and CNS tumors (ADVL1414): A Children's Oncology Group Phase 1 Consortium Trial
Authors: Green Adam L. , Minard Charles G. , Liu Xiaowei , Safgren Stephanie L. , Pinkney Kerice , Harris Lauren , Link Gabrielle , DeSisto John , Voss Stephan , Nelson Marvin D. , Reid Joel M. , Fox Elizabeth , Weigel Brenda J. , Glade Bender Julia
Published: February 2025

Background: Selinexor is a first-in-class, central nervous system (CNS)-penetrant, oral inhibitor of exportin 1 (XPO1), the main nuclear exporter of many key tumor suppressors. We report a phase 1 trial of selinexor in children and adolescents with recurrent CNS and solid tumors (NCT02323880). Methods: A rolling-six design was used to evaluate the maximum tolerated dose (MTD) and first dose pharmacokinetics (PK) of selinexor administered once (QW, 35-45 mg/m2) or twice (BIW, 20-35 mg/m2) weekly during a 28-day cycle (Part A). Ten additional patients with high-grade glioma (HGG) were treated at the QW MTD (Part B). Results: In Part A, 49 patients were enrolled. Continuous BIW dosing was limited by extended hematologic toxicity. The MTD on a BIW schedule for three weeks on/one-week off (BIW 3/1) was 20 mg/m2/dose. Dose-limiting toxicities (DLTs) on this schedule included fatigue, acute reversible neurologic changes, neutropenia, thrombocytopenia, and AST/ALT increase. On a continuous QW schedule, the MTD was 35 mg/m2/dose, DLTs included seizure and thrombocytopenia. In Part B (HGG expansion), there were no additional DLTs observed. Non-dose-limiting toxicity included lymphopenia, leukopenia, neutropenia, thrombocytopenia, anorexia, fatigue, hypophosphatemia, nausea, and vomiting. There were no objective responses. The median number of cycles received was 1 (range 1-9); Eight of 59 patients (13.5%) received 5-9 cycles, five of whom had HGG. Conclusions: Selinexor-related toxicities were primarily hematologic and neurologic requiring dose or dose-frequency reduction. The MTD and recommended initial phase 2 dose of selinexor in children and adolescents with recurrent solid and CNS tumors is 35 mg/m2/dose QW.
Update on Retinoblastoma Predisposition and Surveillance Recommendations for Children
Authors: Kamihara Junne , Schienda Jaclyn , McGee Rose B. , Friedman Danielle Novetsky. , Rednam Surya P. , Brzezinski Jack J. , Kim Sun Young , Becktell Kerri D. , Lupo Philip J. , Gallie Brenda L. , Greer Mary-Louise C. , Hansford Jordan R. , Brodeur Garrett M.
Published: February 2025

Hereditary retinoblastoma is a classic cancer predisposition syndrome with risks beginning in early infancy. About 45% of children with retinoblastoma (RB) have hereditary disease. These children are at risk for both intraocular disease as well as additional neoplasms throughout their lifetime. Germline pathogenic variants (GPVs) in RB1 typically lead to bilateral intraocular disease, elevated risks of trilateral RB, and risks of subsequent malignant neoplasms (non-ocular tumors), especially sarcomas and melanomas. There is further increased risk of subsequent malignant neoplasms if radiation treatment is used. Herein, with a reconvening of the AACR Childhood Cancer Predisposition Workshop, we expand on strategies for identifying individuals with hereditary RB, with a focus on testing strategies for children with RB. We also provide updates from previous recommendations. Given the high penetrance of retinal tumors, we review the importance of close intraocular surveillance and consider recent data regarding surveillance for subsequent malignant neoplasms. Finally, we discuss the importance of counseling for survivors of intraocular disease to address risks of adult-onset tumors as well as to consider reproductive risks.