bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotional Projective Mapping (EmoMap): A Pilot Study Examining a Tool for Collecting Emotional Responses to Food
Authors: Coelho Laura M. , Sharma Madhu , Duizer Lisa
Published: February 2025

Emotions can provide meaningful information for understanding food choices. Most methods for collecting emotions in sensory evaluation are list‐based questionnaires. Lists, however, might reduce data accuracy and lead to lost information. Therefore, an adaptation of projective mapping for collecting emotional responses, called Emotional Projective Mapping (EmoMap) is being piloted. To validate the EmoMap, online, it was compared to two lexicon techniques (EsSense25/emotion circumplex). Pictures of eight foods were presented to 63 participants who answered how they expected to feel if they could eat the food. EmoMap was effective in discriminating and describing foods based on the emotional profile. Twenty‐seven emotion categories were created providing broad descriptive data for a holistic understanding of participants' perceptions. EmoMap can effectively be used to collect product‐specific emotional data in a single session. Data collected were used in an integrative analysis to show an overall relation between emotions, attributes, and liking.
Trisomy 8‐Positive Atypical Neuro‐Behçet's Disease With Recurrent Fever Attacks and Meningitis Over 17 Years
Authors: Hamada Yuichi , Sekiya Tomoko , Nakano Mai , Kida Yuko , Kitano Masayasu , Shibata Masunari , Nishinaka Kazuto
Published: February 2025

Trisomy 8 very rarely causes atypical Behçet's disease without myelodysplastic syndrome (MDS). We report the case of 75‐year‐old woman with trisomy 8 who developed an atypical neuro‐Behçet's disease (NBD) without MDS. She developed aseptic meningitis and ileal ulcers after 17 years of recurrent fever attacks with high C‐reactive protein levels. Despite steroid treatment, her condition deteriorated. Laboratory tests showed human leukocyte antigen (HLA)‐B54, HLA‐Cw1, and a heterozygous E148Q mutation in the MEFV gene. She had no MDS complications. Colchicine and adalimumab were effective. Two years later, pathergy and genital ulcers appeared. We diagnosed NBD based on the symptoms. Chromosomal abnormalities, genetic factors, and HLA typing could influence symptoms and treatment responsiveness.
Oral Leukoplakia Microbiome Predicts the Degree of Dysplasia and is Shaped by Smoking and Tooth Loss
Authors: Galvin Sheila , Honari Bahman , Anishchuk Sviatlana , Healy Claire M. , Moran Gary P.
Published: February 2025

Objective

This study aimed to determine if the oral potentially malignant disorder, oral leukoplakia (OLK), exhibited microbiome changes that predict the degree of dysplasia and the risk of malignant progression.

Results

We examined the microbiome in 216 swabs of OLK from 177 patients. Compared to healthy controls (n = 120 swabs from 61 patients), who were less likely to smoke and had better oral health, OLK patients exhibited an increased abundance of Rothia mucilaginosa, Streptococcus parasanguinis and S. salivarius, resembling acetaldehyde generating communities described previously. Compared to the patients' healthy contralateral normal (CLN) mucosa (n = 202), which acts as a matched control for oral health parameters, OLK exhibited increased S. infantis, Leptotrichia spp., Bergeyella spp., Porphyromonas spp. and F. nucleatum. Machine learning with clinical and microbiome data could discriminate high‐risk dysplasia (moderate to severe) from low‐risk dysplasia (none or mild) (sensitivity 87.4%; specificity 76.5%). Follow‐up swabs were recovered from 58 patients, eight of whom progressed to a higher grade of dysplasia or OSCC and these eight patients exhibited a higher abundance of Fusobacterium species at their initial presentation.

Conclusions

Our study suggests that the OLK microbiome has potential to be an aid to the prediction of dysplasia grade and the risk of malignant transformation.
A comparative diagnostic study using clinical and multimodal assessment, including functional neuroimaging and oculomotricity tools, to differentiate ADHD in young patients from healthy control group
Authors: Ma Guocan , Eng Alexander E. , Chiang Soon‐kiat , Hao Fengyi , McIntyre Roger S. , Zhou Dewen , Yang Ying , Ho Roger C. , Yam Kai Chi
Published: February 2025

Aim

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that may persist into adulthood, with no established objective diagnostic tool yet. This study aims to propose a multimodal objective assessment tool involving clinical assessments, functional neuroimaging, and oculomotricity measurement for ADHD in young adults.

Methods

Seventy‐one medication‐naïve patients and 71 healthy controls (HCs) aged 18 to 28 underwent clinical interviews, Conners' Adult ADHD Rating Scale (CAARS) questionnaire, functional near‐infrared spectroscopy (fNIRS), oculomotricity task, and Conners' Continuous Performance Task (CPT) 3rd edition. Student's t‐tests with Bonferroni's correction were performed to compare the performance between groups, and logistic regression was used for classification.

Results

ADHD patients had significantly lower frontal hemodynamic response during verbal fluency task (VFT) (P = 0.0003), more anticipatory eye movements during overlap task (P = 0.0006), higher latency (P < 0.0001), anticipatory (P < 0.0001), and errors (P < 0.0001) during anti‐saccade task, as well as higher commission errors (P < 0.0001) and standard deviation in hit reaction time (HRT) (P = 0.0018). The multivariate logistic regression model featuring these seven parameters from the three objective tests (fNIRS‐VFT, oculomotricity, and CPT) yielded an area under the receiver operating characteristic curve (AUC) value of 0.892 (95% confidence interval (CI): 0.840–0.944), with sensitivity and specificity of 80.28% and 84.51%, respectively.

Conclusion

This multimodal assessment offered an accurate diagnostic tool for ADHD in young adults and laid the foundation for future machine‐learning approaches.
Two‐year impact of COVID‐19: Longitudinal MRI brain changes and neuropsychiatric trajectories
Authors: Dadsena Ravi , Walders Julia , Costa Ana S. , Wetz Sophie , Romanzetti Sandro , Lischewski Stella Andrea , Krockauer Christina , Heine Josephine , Schlenker Lars , Klabunn Pia , Schwichtenberg Katia , Hartung Tim J. , Franke Christiana , Balloff Carolin , Binkofski Ferdinand , Schulz Jörg B. , Finke Carsten , Reetz Kathrin
Published: February 2025

Aim

Up to 10% of SARS‐CoV‐2 infected individuals suffer from post‐COVID‐19 condition, marked by fatigue and cognitive dysfunction as major symptoms. Longitudinal studies on neuropsychological and clinical trajectories and related brain changes are scarce. Here, we aimed to examine their evolution up to 2 years post‐infection.

Methods

In a multi‐center, longitudinal study of 79 post‐COVID patients (mean age 46, 48 female) with persistent symptoms and 21 age‐ and sex‐matched never‐infected, healthy controls (mean age 42, eight female), we analyzed neuropsychological performance, self‐reported outcomes and associated neuroimaging alterations of resting‐state functional and structural magnetic resonance imaging data 23 months post‐infection.

Results

In post‐COVID patients 23 months after SARS‐CoV‐2 infection we observed (1) that fatigue severity had reduced but still remained present in most patients, (2) widespread brain changes involving the brainstem, the pre‐ and postcentral gyrus and the limbic olfactory network, (3) a weakening of self‐reported fatigue and its cerebral associations. Notably, findings of brain aberrations were more pronounced in hospitalized patients.

Conclusion

Our findings indicate that complex brain adaptations take place up to 2 years following SARS‐CoV‐2 infection. Some regions manifest enduring abnormalities while others undergo restitution. The attenuation of radio‐clinical associations suggests a compensatory function for these regions, pointing to non‐brain intrinsic factors to sustain persistent fatigue.
Incidence and Management of Posttransplantation Lymphoproliferative Disorder After Pediatric Solid Organ Transplantation: The Norwegian Experience
Authors: Aartun Olav Sondre Skorge , Hustveit Karen Henriette , Munthe‐Kaas Monica Cheng , Gjerstad Ann Christin , Bjerre Anna , Østensen Anniken Bjørnstad , Möller Thomas
Published: February 2025

Background

Posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation (SOT) due to immunosuppression. In 2023, a pediatric PTLD register was established in Norway because of a perceived increase in the incidence of pediatric PTLD. This study aimed to analyze population‐based data on the incidence and management of pediatric PTLD after SOT using the pediatric PTLD registry in Norway.

Methods

This retrospective quality assurance study collected the data of pediatric patients with PTLD after SOT in Norway from January 1, 1995, to December 31, 2023. For comparison and calculation of incidence rates, SOT patients without PTLD required a minimum of 1 year posttransplant follow‐up to be included.

Results

A total of 457 patients underwent SOT (57% males) and 22 (4.8%) developed PTLD (73% males). The median age at transplant in the SOT and PTLD groups were 9.5 (interquartile range, 2.4–14.5) and 4.3 (1.1–12.5) years, respectively. Twenty patients with PTLD (91%) were Epstein–Barr virus naive at the time of transplantation. Eighteen (82%) and four (18%) patients developed early and late PTLD, respectively. Ten patients had monomorphic PTLD (45%). All patients received a reduction in immunosuppression, 15 received rituximab, and six required chemotherapy. Six patients (27%) died after PTLD, five of whom had active PTLD disease at the time of death. None of the patients experienced graft loss.

Conclusions

Our findings regarding the incidence, EBV status, sex, and age at transplantation align with those of previous studies.
Reactive oxygen species are involved in inhibition of photoreactivation of Staphylococcus aureus irradiated with 222‐nm Far ultraviolet C
Authors: Fukushi Risako , Narita Kouji , Yamane Kyosuke , Koi Toru , Asano Krisana , Nakane Akio
Published: February 2025

Ultraviolet‐C (UV‐C) at a wavelength of 254 nm is used for disinfection but cannot be used in dwelling space because it is harmful to the human body, while 222‐nm Far UV‐C shows germicidal effect and poses little hazardous effect to human. Formation of cyclobutane pyrimidine dimers (CPD) of DNA is a main mechanism of UV‐C germicidal effect. CPD formed by irradiation with 254‐nm UV‐C is repaired and bacterial proliferation is recovered by photoreactivation. In this study, we investigated photoreactivation of Staphylococcus aureus irradiated with 222‐nm Far UV‐C. The proliferative effect of 222‐nm Far UV‐C irradiated S. aureus by photoreactivation was inferior to that of irradiated with 254‐nm UV‐C. The 254‐nm UV‐C wavelength and 222‐nm Far UV‐C induced CPD in S. aureus cells, and the same level of CPD was repaired in cells irradiated with either UV‐C after photoreactivation. It has been reported that UV‐C induces generation of reactive oxygen species (ROS) in bacteria and that ROS oxidize and inactivate a variety of biomolecules in bacteria. This study showed that more ROS‐producing S. aureus were observed after irradiation with 222‐nm Far UV‐C compared with 254‐nm UV‐C. These results indicate that ROS may be involved in lower recovery of 222‐nm Far UV‐C irradiated S. aureus by photoreactivation.
Heterotrimeric G protein interacts with MLO1 to regulate a trade‐off between disease resistance and growth in wheat
Authors: Zhang Yunwei , Yang Ziyi , Bai Wanqing , Huang Shuxian , Chen Yaoyu , Sun Jiaqiang
Published: February 2025

The molecular mechanisms underlying the balance between disease resistance and growth in wheat remain largely unclear. Here, we report that CRISPR/Cas9‐guided gene‐editing mutants of wheat G alpha subunit exhibit compact plant architecture and enhanced resistance against powdery mildew but with a compromise in yield traits. RNA‐seq analyses show that some growth‐related genes were down‐regulated while some disease resistance‐related genes were up‐regulated in the Tagα‐aabbdd mutant. We demonstrate that the C‐terminal peptide403‐534 of TaMLO1 mediates the interaction with TaGα. Furthermore, TaMLO1 can significantly interfere with the interaction between TaGα and TaGβ. Taken together, we discover the functional association of TaMLO1 and heterotrimeric G protein in regulating a trade‐off between disease resistance and growth in wheat.
Impact of Nigrospora oryzae‐Derived Natural Products on Photosynthesis and Oxidative Stress in Eichhornia crassipes
Authors: Laosinwattana Chamroon , Manichart Nutcha , Wichittrakarn Pattharin , Yoneyama Kaori , Teerarak Montinee , Passara Hataichanok
Published: February 2025

Interest in natural herbicides has been growing due to government policies restricting synthetic herbicide use in many countries. In that regard, this study investigates the potential of Nigrospora oryzae extract as a natural herbicide against the aquatic invasive weed Eichhornia crassipes. A stable formulation was developed with a droplet size of 36.44 ± 0.36 nm and a zeta potential of ‐62.59 mV. Pot‐based experiments revealed the N. oryzae extract induced 38.33% phytotoxicity within 24 hours, increasing to 84.72% by 28 days post‐treatment. Scanning electron microscopy demonstrated morphoanatomical changes in epidermal tissue and stroma of E. crassipes, such as erosion of epicuticular waxes and degeneration of epidermis cells. The treatment significantly reduced the photosynthetic pigment content while increasing hydrogen peroxide (46.26%), malondialdehyde (17.49%), and proline (19.16%) levels, causing cellular electrolyte leakage. Activities of superoxide dismutase, catalase, ascorbate peroxidase, and guaiacol peroxidase were significantly elevated (p<0.05), indicating oxidative damage. These findings demonstrate that N. oryzae extract can disrupt growth and photosynthesis and induce oxidative stress in E. crassipes, suggesting its potential as a source of natural herbicide for industrial application.
Late‐life parkinsonism in bipolar disorder
Authors: Nishio Yoshiyuki , Amemiya Kiyomi , Oyama Jun
Published: February 2025

Aim

Parkinsonism is a frequently encountered symptom in individuals with bipolar disorder (BD). It can be drug‐induced, co‐occurring with Parkinson's disease (PD), or a genuine motor abnormality of BD itself. This study aims to address the primary pathophysiology of parkinsonism in BD.

Methods

Sixteen patients with BD and parkinsonism were recruited from consecutive patients who were referred to a neurology clinic at a tertiary psychiatric centre. The patients underwent clinical assessments, dopamine transporter single‐photon computed tomography (DAT‐SPECT), cardiac 123I‐metaiodo‐benzylguanidine (MIBG) scintigraphy, and morphometric magnetic resonance imaging (MRI). The positivity or negativity of Lewy body disease (LBD) biomarkers was determined based on the visual assessment of DAT‐SPECT and heart‐to‐mediastinum ratio on cardiac MIBG scintigraphy. Four out of the 16 participants received 300‐600 mg of levodopa.

Results

Thirteen patients were diagnosed with BD type 1, and 12 had experienced >5 previous mood episodes. Parkinsonism developed more than 10 years after the onset of BD and after the age of 50 years in all patients. Four cases were positive for LBD biomarkers. Six patients with negative LBD biomarkers showed reduced striatal uptake with z‐scores below −2.0. MRI morphometry revealed varying degrees of brain atrophy in most patients. Three of the four patients did not respond to 600 mg of levodopa.

Conclusions

The results of this study indicate that the majority of parkinsonism observed in BD is not a consequence of PD/LBD. Instead, it may represent a genuine motor abnormality of BD in late life.
Dissipative Gradient Nonlinearities Prevent δ$\delta$‐Formations in Local and Nonlocal Attraction–Repulsion Chemotaxis Models
Authors: Li Tongxing , Acosta‐Soba Daniel , Columbu Alessandro , Viglialoro Giuseppe
Published: February 2025

We study a class of zero‐flux attraction–repulsion chemotaxis models, characterized by nonlinearities laws for the diffusion of the cell density , the chemosensitivities and the production rates of the chemoattractant and the chemorepellent . In addition, a source involving also the gradient of is incorporated. Our overall study touches on different aspects: we address questions connected to local well‐posedness, we derive sufficient conditions to ensure boundedness of solutions, and finally, we develop numerical simulations giving insights into the evolution of the system.
Introducing the suicide prevention trials database: A publicly available data repository of suicide prevention studies
Authors: O'Neil Maya E. , Veazie Stephanie , Krushnic Danielle , Hannon Sara , Baker‐Robinson William , Adams Joren , Clauss Kate , Constans Joseph , Hamblen Jessica L. , Somohano Vanessa C. , Denneson Lauren M.
Published: February 2025

Background

Healthcare, research, policy, and legislative stakeholders need timely, accurate, and detailed information on the effectiveness and potential harms of suicide prevention approaches. We created the Suicide Prevention Trials Database (SPTD) to provide a centralized, publicly accessible, detailed database of harmonized study‐level suicide prevention clinical trial data.

Methods

We searched for randomized controlled trials (RCTs) of suicide prevention published from 1980 to 2023. Over 300 data variables were extracted from each RCT.

Results

We identified a total of 140 unique RCTs in 180 articles. Most of the included RCTs compared two treatment arms (92%), and the remainder compared three arms (88%). Nearly half of the RCTs reported on Behavioral Interventions (49%), followed by Care Management, Follow‐up, or Monitoring (16%). Typically, the comparator condition was Treatment as Usual (53%). Interventions were most often delivered in person (61%) in an individual format (79%).

Conclusions

The SPTD provides efficient, accurate, up‐to‐date access to a comprehensive suicide prevention trials database, which can be utilized by a range of stakeholders. It can reduce the time required for high‐quality systematic reviews and provides researchers, administrators, and funders with current data on the state of the literature.
Teacher leadership for integrated STEM education: Identifying what effective leaders need to know and do
Authors: Stevenson Emma , Thompson Pauline
Published: February 2025

Internationally, science, technology, engineering, mathematics (iSTEM) education continues to flourish in schools, with many now embracing the combined disciplinary assumption suggested by its acronym; integrated STEM (iSTEM) education. Advocated for its potential to increase student interest and achievement in STEM subjects, courses, and careers, leadership in iSTEM education is beneficial for promoting its success in schools. However, there is limited understanding of the characteristics of effective iSTEM teacher leaders. Seeking to provide greater insight into iSTEM teacher leadership, the research question addressed in this study is: What are the characteristics of iSTEM teacher leaders? This qualitative study explored teacher leaders' perceptions of the characteristics valuable for supporting iSTEM education in schools. Data collected involved semi‐structured interviews with five teachers implementing and leading iSTEM education. Findings identify the importance of iSTEM education‐specific characteristics such as disciplinary knowledge and creating iSTEM teaching resources. Differences between leaders revealed the importance of considering contextual needs and capabilities. This paper discusses the identified characteristics and their importance in supporting iSTEM progression in schools, providing valuable insight for school principals and those designing leadership programs for teachers, as well as suggestions for further research.
Developing teacher leader efficacy to address attrition
Authors: Lin Joyce , Galosy Jodie , Ross Carolyn , Watts Jessica , Wilson Gina
Published: February 2025

Research shows that 44% of new teachers quit teaching within the first 5 years. This study aims to explore the link between teacher leadership and the retention of science and math teachers and contributes to the increasing body of research suggesting that teacher leadership could be a promising way to tackle the problem of retaining teachers in our country. Drawing on survey data from a 5‐year teaching fellowship program serving beginning high school math and science teachers, we propose that teacher leader efficacy, or the extent to which a teacher believes they have the capacity to improve education beyond their own classroom, can be a promising mediator that supports retention. We investigate how expanding teachers' views of leadership and developing and sharing practitioner knowledge can enhance teacher leader efficacy and improve teacher retention. Our findings shed light on the connection between teacher leadership efficacy and retention, emphasizing the importance of leadership models and practitioner inquiry in developing teacher leadership efficacy. We end by discussing implications for others supporting teacher leadership and teacher retention or conducting research in these areas.
Identification of the Novel HLA‐DRB3*02:213 Allele by Next‐Generation Sequencing
Authors: Bouthemy Charlène , Milhès Jean , Congy‐Jolivet Nicolas
Published: February 2025

HLA‐DRB3*02:213 differs from DRB3*02:02 by one nucleotide substitution in codon 6 in exon 2.
Discovery of the Novel HLA‐DQB1*04:104 Allele Using Short‐ and Long‐Read Sequencing Technologies
Authors: Santos Angela , Mendes‐Oliveira Victoria , Vianna Romulo , Porto Luís Cristóvão , Secco Danielle
Published: February 2025

The novel HLA‐DQB1*04:104 allele, first described in an individual from Brazil.
Next Generation Sequencing Reveals A Novel HLA‐C Allele, HLA‐C*07:1172
Authors: Rakhmanov Mirzokhid , Bernheiden Martin , Verboom Murielle , Hallensleben Michael , Emmerich Florian
Published: February 2025

HLA‐C*07:1172 differs from HLA‐C*07:01:01:01 by a single nucleotide substitution in Codon 7 in Exon 2.
Implementing an Escape Room for Clinical Skills Practice in a Paediatrics Clerkship
Authors: Khera Sofia , Wai Andrew , Ford Christine , Yoo Andrew , Joe Daniel , Oyoyo Udochukwu
Published: February 2025

Background

Escape rooms include the same experiential learning methods that make traditional simulation practices effective while adding gamification which improves learner engagement. Our existing simulation curriculum lacked active experimentation, an essential component of Kolb's experiential learning cycle. The goal of this curriculum innovation was to determine the feasibility of adding an escape room immediately following the simulation to provide an effective independent learning experience for learners.

Approach

We created a 40‐min escape room activity using principles of self‐determination theory. All students in the paediatric clerkship participated once over one academic year. Students were presented with an unstable child with seizures and worked in teams of 3–5 to open locks and solve puzzles as they applied nine clinical skills learned from the preceding simulation session.

Evaluation

Students (N = 66) reported increases in knowledge after both the simulation and the escape room and an increase in confidence after completing the escape room, indicating we were successful in adding active experimentation to our curriculum. They also commented on the value of applying and practising new skills and of engaging in teamwork, which reinforced the utilization of self‐determination theory as a guiding principle for escape room design.

Implications

Our escape room is novel in that it takes place in a paediatric clerkship setting and builds upon existing curricular elements to provide students with independent practice of clinical skills in a gamified and fun approach early in their clinical training years. Escape rooms are a feasible and an effective method to provide hands‐on experience to clinical learning.
Inhibition of BK channels by GABAb receptors enhances intrinsic excitability of layer 2/3 vasoactive intestinal polypeptide‐expressing interneurons in mouse neocortex
Authors: Bogaj Karolina , Urban‐Ciecko Joanna
Published: February 2025

GABAb receptors (GABAbRs) affect many signalling pathways, and hence the net effect of the activity of these receptors depends upon the specific ion channels that they are linked to, leading to different effects on specific neuronal populations. Typically, GABAbRs suppress neuronal activity in the cerebral cortex. Previously, we found that neocortical parvalbumin‐expressing cells are strongly inhibited through GABAbRs, whereas somatostatin interneurons are immune to this modulation. Here, we employed in vitro whole‐cell patch‐clamp recordings to study whether GABAbRs modulate the activity of vasoactive intestinal polypeptide‐expressing interneurons (VIP‐INs) in layer (L) 2/3 of the mouse primary somatosensory cortex. Utilizing machine learning algorithms (hierarchical clustering and principal component analysis), we revealed that one VIP‐IN cluster (about 68% of all VIP‐INs) was sensitive to GABAbR activation. Paradoxically, when recordings were performed in standard conditions with high extracellular Ca2+ level, GABAbRs indirectly inhibited the activity of large conductance voltage‐ and calcium‐activated potassium (BK) channels and reduced GABAaR‐mediated inhibition, leading to an increase in intrinsic excitability of these interneurons. However, a classical inhibitory effect of GABAbRs on L2/3 VIP‐INs was observed in modified artificial cerebrospinal fluid with physiological (low) Ca2+ concentration. Our results are essential for a deeper understanding of mechanisms underlying the modulation of cortical networks.

image

Key points

Layer 2/3 vasoactive intestinal polypeptide‐expressing interneurons (VIP‐INs) in the mouse somatosensory cortex cluster into three electrophysiological types differentially sensitive to GABAb receptors (GABAbRs).

The majority of VIP‐INs (type 1, about 68% of all VIP‐INs) are regulated through pre‐ and postsynaptic GABAbRs, while a subset of these interneurons (types 2 and 3) is controlled only presynaptically.

The net effect of GABAbR activation on VIP‐IN excitability depends on [Ca2+] in artificial cerebrospinal fluid.

When [Ca2+] is high (2.5 mM), GABAbRs indirectly inhibit BK channels and reduce GABAaR inhibition leading to increased intrinsic excitability of type 1 VIP‐INs.

When [Ca2+] is low (1 mM), which is more physiological, BK channels do not regulate the intrinsic excitability of VIP‐INs and thus postsynaptic GABAbRs canonically decrease the intrinsic excitability of type 1 VIP‐INs.
Surface Modification of LPBF Ti6Al4V Through In Situ Nitrogen-Assisted Laser Surface Remelting
Authors: Porwal Ankit , Dhara Santanu , Kumar Cheruvu Siva
Published: February 2025

Laser surface remelting is a widely used method for surface modification of titanium and related alloys, particularly to enhance its workability in the biomedical industry through surface nitriding. The present work aims to develop the nitride surface over the laser powder bed fusion (LPBF)-processed Ti6Al4V substrate by introducing the nitrogen environment in the build chamber during the remelting. The effects of different laser power and laser scan speeds were studied over the surface topography and elemental changes of the remelted surface. The result shows an increase in surface roughness with selective laser remelting, which could enhance cell proliferation or osseointegration, which is advantageous for biomedical applications. Energy-dispersive X-ray (EDX) results show a significant increase in nitrogen content in terms of weight percentage for the in situ remelted surface. X-ray diffraction (XRD) phase analysis shows the presence of titanium (Ti) and aluminum (Al) nitride peaks, and X-ray photon-electron spectrometry (XPS) also indicates the formation of nitrogen bonds with Ti and Al, which were initially missing in the substrate. The results reported here confirm the nitride surface formation over the substrate due to the in situ remelting under the nitrogen environment for the LPBF-processed Ti6Al4V, which could be used for improved biomedical applications.
Motor Competence Assessment: Adaptation for Children With Autism Spectrum Disorder
Authors: Dionisio Jadiane , Sá Cristina dos Santos Cardoso de , Luz Carlos , Silva Bruno , Rodrigues Luis Paulo , Cordovil Rita
Published: February 2025

This study aims to adapt the Motor Competence Assessment (MCA) instrument for autistic children. The adaptation was carried out in three stages: (a) a pilot test, (b) MCA assessment of 45 children with autism (Levels I and II) aged 5–11 years with documentation of each MCA test difficulties, and (c) adaptations to the original MCA tests were discussed with the original MCA authors, to decide each test adaptation. Ten items from the MCA were adapted, namely: manipulative tasks—throwing and kicking distance at 3 m; stabilizing tasks—rubberizing the feet of the wooden platform and initially grabbing the platform with one hand; scoring the jumping sideways test even when the feet do not land simultaneously; and locomotor tasks—placing in the floor the second wooden block in the shuttle run task, and in the standing long jump task, adding a line to be used as guide for the jump direction. The adaptation of the MCA proved to be of great scientific value and beneficial to health care and education professionals by providing them with access to a low-cost, efficient, reliable, and quantitative tool for assessing and monitoring the motor competence of children with autism.
Rebuilding duct work from the gallbladder
Authors: Wong Wei
Published: February 2025

Smooth muscle cells from the gallbladder induce retinoic acid signaling to promote repair of intrahepatic biliary ducts.
Efficacy and safety of switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low-level viremia: a real-world 48-week extension study
Authors: He Meng-Wen , Cui Li , Chen Dan-Dan , Zhao Yun , Luo Wen-Zhao , Jia Yun-Fei , Zhou Jie , He Qing-Juan , Dai Ying , Zhang Wei-Hua , Yu Zhao-Xia , Wang Wen-Chang , Guo Chang , Fu Yi-Ming , Yang Wu-Cai , Li Xu-Yang , Guo Yi-Fan , Wang Chun-Yan , Wang Jian-Jun , Li Ping , Qiao Bing , Ji Dong , Li Zhong-Bin
Published: February 2025

Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group (
P
< 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.

CLINICAL TRIALS

This study is registered with the Chinese Clinial Trial Registry as
ChiCTR2400089257
.
Contribution of the gonococcal
NEIS1446-ispD
gene conversion to the pathobiology of the
Neisseria meningitidis
urethritis clade,
Nm
UC
Authors: Rodriguez Emilio I. , Tzeng Yih-Ling , Sannigrahi Soma , Stephens David S.
Published: February 2025

Over the last decade, a
Neisseria meningitidis
(
Nm
) urethritis-causing clade (
Nm
UC) has emerged to cause clusters of meningococcal urethritis in the United States and globally. One genomic signature of
Nm
UC is the integration of
Neisseria gonorrhoeae
(
Ng
) DNA in an operon,
NEIS1446-NEIS1438
, which partially replaced the
Nm ispD
gene. IspD is the 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase of the terpenoid precursor synthesis pathway, required for the production of ubiquinones of the electron transfer chain. IspD is essential in several gram-negative bacteria. The biological importance of the
NEIS1446-ispD
gene conversion event for
Nm
UC was investigated. The
ispD
gene was found to be essential in
Nm
UC (CNM3) and non-clade
Nm
(MC58), and a mutation at the native locus can only be made with the insertion of a second
ispD
copy in the genome. The IspD
MC58
variant was more efficient at promoting aerobic growth at a low level than IspD
CNM3
; the two proteins differ by 15 residues. Maximal aerobic growth densities of strains with an
Nm
UC background resembled
Ng
(FA19), and both were significantly lower than
Nm
. In contrast to non-clade
Nm
, all
Nm
UC strains survived well anaerobically. Increasing
ispD
expression by titrating IPTG in non-clade
Nm
enhanced anaerobic survival. Translational reporters of the
Nm
UC and
Ng
promoters demonstrated similar expression levels, and both were significantly higher than non-clade
Nm
, under aerobic and microaerobic conditions. Our findings suggest that the integration of gonococcal DNA into the
NEIS1446-NEIS1438
operon of
Nm
UC has increased
ispD
expression
,
contributing to
Nm
UC’s adaptation to the oxygen-limited environment of the human urogenital tract.
Genome-wide analysis of
Enterococcus faecalis
genes that facilitate interspecies competition with
Lactobacillus crispatus
Authors: Lam Ling Ning , Savage Kathryn E. , Shakir Camille N. , Lemos José A.
Published: February 2025

Enterococci are opportunistic pathogens notorious for causing a variety of infections. While both
Enterococcus faecalis
and
Lactobacillus crispatus
are commensal residents of the vaginal tract, the molecular mechanisms that enable
E. faecalis
to take advantage of a vaginal biome with lower counts of lactobacilli to colonize the vaginal tract and induce aerobic vaginitis remain unknown. Here, we show that
L. crispatus
eradicates
E. faecalis
in a contact-independent manner. Using transposon sequencing to identify
E. faecalis
OG1RF transposon (Tn) mutants that are either under-represented or over-represented when co-cultured with
L. crispatus
, we found that Tn mutants with disruption in the
dltABCD
operon, that encodes the proteins responsible for the D-alanylation of teichoic acids, and
OG1RF_11697
encoding for an uncharacterized hypothetical protein are more susceptible to killing by
L. crispatus
. Inversely, Tn mutants with disruption in
ldh1,
which encodes for L-lactate dehydrogenase, are more resistant to
L. crispatu
s killing. Using the
Galleria mellonella
infection model, we show that co-injection of
L. crispatus
with
E. faecalis
OG1RF enhances larvae survival while this
L. crispatus
-mediated protection was lost in larvae co-infected with either
L. crispatus
and
E. faecalis
Δ
ldh1
or Δ
ldh1
Δ
ldh2
strains. Last, using RNA sequencing to identify
E. faecalis
genes that are differently expressed in the presence of
L. crispatus
, we found major changes in the expression of genes associated with glycerophospholipid metabolism, central metabolism, and general stress responses. The findings in this study provide insights into how
E. faecalis
mitigate assaults by
L. crispatus
.

IMPORTANCE

Enterococcus faecalis
is an opportunistic pathogen notorious for causing a multitude of infections. As vaginal commensals,
E. faecalis
must interact with
Lactobacillus crispatus
, but how
E. faecalis
overcomes or mitigate assaults by
L. crispatus
killing remains unknown. We show that
L. crispatus
eradicates
E. faecalis
temporally in a contact-independent manner. Using high-throughput molecular approaches, we identified genetic determinants that enable
E. faecalis
to compete with
L. crispatus
. This study represents an important first step for the identification of adaptive genetic traits required for enterococci to tolerate assaults by lactobacilli.
Targeting Ikaros and Aiolos with pomalidomide fails to reactivate or induce apoptosis of the latent HIV reservoir
Authors: Pascoe Rachel D. , Kim Youry , Rhodes Ajantha , Ong Jesslyn , Tumpach Carolin , Gubser Celine , Chang J. Judy , McMahon James H. , Lewin Sharon R. , Rasmussen Thomas A.
Published: February 2025

HIV persists in people living with HIV (PLHIV) on antiretroviral therapy (ART) in long-lived and proliferating latently infected CD4+ T cells that selectively express pro-survival proteins, including the zinc finger proteins, Ikaros and Aiolos. In this study, we investigated whether pomalidomide, an immunomodulatory agent that induces degradation of Ikaros and Aiolos, could increase the death of HIV-infected cells and/or reverse HIV latency. Using an
in vitro
model of CD4+ T cells infected with a green fluorescent protein (GFP) reporter virus, pomalidomide increased the expression of the pro-survival protein B cell lymphoma (Bcl)-2 and did not increase apoptosis of GFP+ HIV productively infected CD4+ T cells. Pomalidomide also increased the expression of CD155 and UL16-binding protein (ULBP) stress proteins on GFP+ HIV productively infected CD4+ T cells, but this did not translate to enhanced clearance following co-culture with a natural killer (NK) cell line. Using CD4+ T cells from PLHIV on ART, pomalidomide
ex vivo
activated memory CD4+ T cells resulting in elevated HLA-DR expression and induced CD4+ T cell proliferation but only in the presence of T cell receptor stimulation with anti-CD3 and anti-CD28. There was no effect on cell-associated HIV RNA or the frequency of intact HIV DNA. In conclusion, despite an increase in stress protein expression, promoting Ikaros and Aiolos degradation in CD4+ T cells using pomalidomide did not directly induce apoptosis of HIV-infected cells or induce HIV latency reversal.

IMPORTANCE

People living with HIV (PLHIV) require lifelong antiretroviral therapy (ART) due to the persistence of latently infected cells. The zinc finger proteins, Ikaros and Aiolos, have recently been implicated in promoting the persistence of latently infected cells. In this study, we investigated the effects of pomalidomide, an immunomodulatory imide drug that induces the degradation of Ikaros and Aiolos, on HIV latency reversal and death of infected cells. Using CD4+ T cells from people living with HIV on suppressive antiretroviral therapy, as well as an
in vitro
model of productive HIV infection, we found that pomalidomide induced T cell activation and expression of stress proteins but no evidence of latency reversal or selective death of infected cells.
RAF1 promotes successful human cytomegalovirus replication and is regulated by AMPK-mediated phosphorylation during infection
Authors: Dunn Diana M. , Pack Ludia J. , Munger Joshua C.
Published: February 2025

RAF1 is a key player in growth factor receptor signaling, which has been linked to multiple viral infections, including human cytomegalovirus (HCMV) infection. Although HCMV remains latent in most individuals, it can cause acute infection in immunocompromised populations, such as transplant recipients, neonates, and cancer patients. Current treatments are suboptimal, highlighting the need for novel therapies. Multiple points in the growth factor signaling pathway are important for HCMV infection, but the relationship between HCMV and RAF1, a component of the mitogen-activated protein kinase (MAPK) cascade, is not well understood. The AMP-activated protein kinase (AMPK) is a known regulator of RAF1, and AMPK activity is induced by HCMV infection, which is important for productive HCMV replication. Our data indicate that HCMV infection induces AMPK-specific changes in RAF1 protein phosphorylation, including increasing phosphorylation at RAF1-Ser621, a known AMPK phospho-site, which results in increased binding to the 14-3-3 scaffolding protein, an important aspect of RAF1 protein activation. Inhibition of RAF1, either pharmacologically or via shRNA or CRISPR-mediated targeting, inhibits viral replication and spread in both fibroblasts and epithelial cells. Collectively, our data indicate that HCMV infection and AMPK activation modulate RAF1 activity, which is important for viral replication.

IMPORTANCE

Human cytomegalovirus (HCMV) infection is a widespread infection impacting approximately 60–90% of the global population. Although latent in healthy individuals, acute infection in immunocompromised populations, such as neonates, transplant recipients, and cancer patients, can result in retinal and gastrointestinal problems, hearing loss, and even death. Current antivirals are suboptimal due to the development of viral resistance or toxicity in patients, highlighting the need for novel treatments. Our research suggests a new potential target, RAF1, which is a regulator of cellular growth and proliferation. We find that RAF1 is phosphorylated by AMP-activated protein kinase, and that inhibition of RAF1 negatively impacts viral infection. Furthermore, drugs currently used to treat certain cancers also inhibit RAF1 and may have an additional anti-HCMV therapeutic effect in HCMV-susceptible cancer patients.
Regulation of IL-10 production in dendritic cells is controlled by the co-activation of TLR2 and Mincle by
Lactiplantibacillus plantarum
OLL2712
Authors: Sakabe Ryuhei , Onishi Kazumasa , Mochizuki Junko , Toshimitsu Takayuki , Shimazu Tomoyuki , Kishino Shigenobu , Ogawa Jun , Yamasaki Sho , Sashihara Toshihiro
Published: February 2025

We showed that
Lactiplantibacillus plantarum
OLL2712 (OLL2712) strongly induces interleukin (IL)-10 production in immune cells. Although beneficial effects of this strain have been observed in both mice and humans, the mechanisms underlying IL-10 induction remain unclear. In this study, we found that OLL2712 co-activates two pattern recognition receptors, leading to IL-10 production in the mouse-derived thermosensitive dendritic cell line, tsDC. We first revealed the involvement of the Toll-like receptor (TLR)2-Myeloid differentiation primary response gene (MYD) 88 pathway in OLL2712-induced IL-10 production in tsDCs. However, stimulation with the TLR2 agonist alone was insufficient to induce IL-10 production. Consequently, we explored additional signaling pathways and found that the phosphorylation of spleen tyrosine kinase (Syk) was important in response to OLL2712, which was not triggered by a TLR2 agonist alone. Notably, the activation of Syk was found to depend on macrophage-inducible C-type lectin receptor (Mincle), one of the C-type lectin receptors. However, the surface-expressed Mincle is not responsible for the IL-10 production by OLL2712. Instead, it depends on the incorporation of OLL2712 into tsDCs, suggesting that Mincle recognizes incorporated OLL2712 intracellularly. In summary, OLL2712 is initially recognized by TLR2, which subsequently induces the expression of Mincle to recognize incorporated OLL2712, ultimately inducing IL-10 production.

IMPORTANCE

The objective of this study is to elucidate the mechanism by which
Lactiplantibacillus plantarum
OLL2712 (OLL2712), previously identified by our research group as a potent stimulator of interleukin-10 production in immune cells, exerts its immunomodulatory effects. Our findings indicate that OLL2712 acts in synergy with two pattern-recognition receptors: Toll-like receptor 2 and Macrophage inducible C-type lectin receptor (Mincle). Additionally, we observed that OLL2712 needs to be internalized intracellularly to be recognized by Mincle. These findings represent the first insights into the detailed mechanism underlying the anti-inflammatory effects of OLL2712.
Pathogenic bacterial taxa constitute a substantial portion of fecal microbiota in common migratory bats and birds in Europe
Authors: Poosakkannu Anbu , Xu Yanjie , Suominen Kati M. , Meierhofer Melissa B. , Sørensen Iben H. , Madsen Jesper J. , Plaquin Betty , Guillemain Matthieu , Joyeux Emmanuel , Keišs Oskars , Lilley Thomas M. , Lehikoinen Aleksi , Pulliainen Arto T.
Published: February 2025

Identifying the wildlife reservoirs of bacterial pathogens, spatially and temporally, is important for assessing the threats to human and the rest of the biosphere. Our objective was to study Europe-wide characteristics of the fecal microbiota of four highly mobile migratory vertebrates, that is, one bat (
Pipistrellus nathusii
) and three bird species (
Turdus merula
,
Anas platyrhynchos
,
Columba palumbus
). The 351 sample PacBio data set of almost the entire 16S rRNA gene with 438,997 amplicon sequence variants (ASVs) assigned 3,277 bacterial species. A significant proportion of the ASVs were assigned to bacterial genera having species pathogenic to human or animals. These pathogen ASVs accounted for 45% of all the ASVs and statistically were more frequent at higher latitudes and in younger age groups. In 36 samples, more than >90% of all the PacBio reads were assigned to these pathogenic genera. We designate to individuals of these samples a new term, that is, a pathogen bloomer. The pathogen bloomers, which did not display apparent macroscopic disease symptoms, were detected in Nathusius bat (
n
= 8; Finland and Latvia), blackbird (
n
= 6; Finland, Latvia and Denmark), and wood pigeon (
n
= 22; Finland and France), but not in mallard. Key species-level taxonomic assignments in the pathogen bloomers were the two well-known enteropathogens (
Campylobacter jejuni
or
Escherichia coli
) and one emerging enteropathogen (
Escherichia marmotae
). Our data imply that the studied common migratory vertebrates may contribute to the transmission of bacterial pathogens across the European continent.

IMPORTANCE

The understanding of gut microbiota composition and dynamics in wild vertebrate populations, especially in highly mobile vertebrates, birds and bats, remains limited. Our study sheds light on the critical knowledge gap in how common pathogenic bacterial taxa of fecal microbiota are in migratory bats and birds in Europe. We found out that bacterial genera having species pathogenic to human or animals constituted a substantial portion of the fecal microbiota in all the studied host taxa. Most importantly, we identified asymptomatic individuals that were dysbiotic with bacterial pathogen overgrowth. These previously unknown pathogen bloomers appear as potent Europe-wide transmitters of bacterial pathogens, which cause, for example, diarrhea and bacteremia in human. Our findings may contribute to better understanding of seasonal disease hotspots and pathogen spillover risks related to migratory vertebrates.