bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactive 3D Objects Enhance Scientific Communication of Structural Data
Authors: Mokos Daniel , Daniel Bastian
Published: February 2025

In scientific communication about three‐dimensional structures, creating two‐dimensional representations is standard practice. These representations often suffer from the drawback of losing potential information due to dimensionality reduction. Several options exist to present, share and publish 3D figures, however based on recent publications they are not widely utilized. Here we present simple ways to preserve the three‐dimensionality of the structure by the creation of a custom‐made model in GLTF format that is generated in the same workflow as the conventional figures. They can be published alongside a given manuscript with minimal additional effort to the authors, but a huge impact on the communicative power of the manuscript concerning the three‐dimensional features of the reported structures. The scripts we adapted and published for this purpose open up new possibilities for the illustrator and allow the viewer to access the full three‐dimensionality of the published structure. In future, this can simplify the publication process of protein structures or other models and be a valuable tool for scientific communication in digital or printed form.
Isolated Growth Hormone Deficiency IA due to a Novel Homozygous Large Deletion ∼1.6 kb Spanning Exons 1–4 of GH1 Gene: A Case Report
Authors: Noorian Shahab , Soltani Hedieh , Aghamahdi Fatemeh , Savad Shahram , Alan Mahnaz Seifi
Published: February 2025

Isolated growth hormone deficiency (IGHD) IA is inherited autosomal recessively and occurs due to GH1 gene deletions. This study emphasizes the importance of clinical diagnosis and molecular examination for detecting novel mutations to prevent misdiagnosis and to consider timely and appropriate management of the current and long‐term consequences of the defect, such as additional deficiencies. We report a male infant who initially presented with a growth delay (‐4SD) at 4 months old, and at 16 months old, was referred to our endocrinology department. Physical examination revealed developmental delay, macrocephaly, head lag, loose body, large head circumference, low and flat nasal bridge, forehead protuberance, three‐pronged fingers, shortness of the hands and feet joints, small palms and plantar, small penises, delayed tooth eruption, and disability to walk. His hormonal tests showed normal free T4 (14.08 pmol/L), upper limit TSH level (5.41 μIU/mL), normal random cortisol 8 AM (250.53 μg/mL), mild high ACTH level (79.6 pg/mL), low IGF1 (13.0) and fasting GH (0.03 ng/mL). GH (ng/mL) maximal response to the arginine test was < 0.05. Whole Exome Sequencing, Polymerase Chain Reaction (PCR), and Quantitative Real‐Time PCR were performed on a peripheral blood sample obtained from the patient. The infant was found to have a homozygous large deletion of approximately 1.6 kb spanning the GH1 gene, which contained exons 1–4 with an autosomal recessive inheritance and a heterozygous deletion of exons 1–4 of GH1 in the parents and homozygous wild‐type in the sibling. Novel mutations in the GH‐1 gene cluster are considered an important cause of idiopathic congenital IGHD. As a result, the role of gene sequencing, besides considering clinical features, should not be neglected.
Transnationalism and the International Counseling Student: An Interpretative Phenomenological Approach
Authors: Behl Malvika , Harrichand John J. S.
Published: February 2025

International counseling students (ICSs) face unique challenges with transnationalism in counselor education programs. This study, including 14 participants, employed interpretative phenomenology to examine the impact on their sociopolitical adjustment in the United States. It revealed significant concerns, including racism, discrimination, microaggression, navigating immigration laws, and the need for advocacy.
Fine Tuning of Hybridized Local and Charge‐Transfer Excited States and Luminescence in Carbazole/Benzothiadiazole Isomeric Emitters by Varying Linking Mode
Authors: Xie Lijuan , Dai Hao , Liu Di , Li Jiuyan , Jin Jing , Wang Jiahui
Published: February 2025

Hybridized local and charge‐transfer (HLCT) type emitters can harvest triplet excitons for light emission via high‐lying reverse intersystem crossing (hRISC), showing great potential for application in organic light‐emitting diodes (OLEDs). Herein, two isomeric emitters NPC3BTD and NPC2BTD were developed by linking two 9‐phenyl‐9H‐carbazole (NPC) donors onto the central benzo[c][1,2,5]thiadiazole (BTD) acceptor. By tuning the linkage from 3‐site to 2‐site of carbazole ring, the D‐A dihedral angle was decreased, then the HOMO delocalization and CT/LE content ratio in HLCT excited states were reduced, thus NPC2BTD revealed fluorescence hypsochromic shift by 30 nm to green region. Simultaneously, the molecular rigidity was increased and non‐radiative transition was suppressed, thus the photoluminescence quantum yield was increased to about 90%. Their HLCT excited state nature was verified by the natural transition orbitals results and detection of two different excited dipole moments in various solvents. It is supposed the hRISC occur from T2 to S1 states. Yellow and green doped OLEDs of NPC3BTD and NPC2BTD exhibited external quantum efficiencies of 5.31% and 5.79% with exciton utilization efficiency of 36.12% and 32.42%. The superior performance of NPC2BTD over NPC3BTD was attributed to the finely tuned HLCT excited states through structure isomerization.
Multi‐modal Homogeneous Chemical Reaction Performance Prediction with Graph and Chemical Language Information
Authors: Wang Shen , Zhao Weiren , Liu Yining , Li Yang
Published: February 2025

Comprehensive Summary

Accurate prediction for chemical reaction performance offers optimal direction for synthetic development. To this end, we present a novel multi‐modal model called MMHRP‐GCL to achieve the prediction of homogeneous chemical reaction yield, enantioselectivity, and activation energy by fusing the information from the text and graph modalities, requiring only 8 simple descriptors and Reaction SMILES obtained without high‐cost DFT computation, and capable of managing reactions involving a fluctuating number of molecules. Experimental results on 4 datasets show that MMHRP‐GCL outperforms at least 7 generalized SOTA methods. Ablation study confirms the critical roles of the complementation of graph and text modalities, as well as the significance of modality alignment and atomic features in prediction. Albeit there is still room for improvement in the interpretation of atomic relationships, the model has a remarkable ability to identify important atoms. A statistically interpretable study of the feature importance and a test on challenging dataset further demonstrates the utility and potential of the model. As a high‐accuracy, low‐cost, interpretable, and general multi‐modal model, MMHRP‐GCL provides valuable guidance on the design of forward predictors for homogeneous catalytic reactions.
Investigate of LOC101928988 Regulatory Effect on the DAPK2 Transcription in Breast Tumors
Authors: Saberiyan Mohammadreza , Ghasemi Nazila , Jafari Negar , Sadeghi Mahboubeh , Ghaderi Abbas , Mousavi Pegah
Published: February 2025

Background

The World Health Organization has mentioned breast cancer holds the highest incidence rate among all types of cancer globally. Death‐associated protein kinase 2 (DAPK2) is a serine/threonine kinase linked to various forms of malignancy, such as breast cancer. This protein assumes a pivotal function in a multitude of cellular mechanisms, including apoptosis, autophagy, and cell migration.

Aims

This study aimed to study the LOC101928988 regulatory effect on the DAPK2 expression in breast cancer.

Methods

In this study, 38 paired tumoral and normal tissues were selected from patients. Quantitative real‐time PCR was used to analyze the expression of DAPK2 and LOC101928988. The interactions of DAPK2 and its intermediate elements with LOC101928988 were predicted by docking analysis.

Results

The expression of DAPK2 and LOC101928988 was downregulated in tumor tissues compared to the control group. Further analysis revealed a significant positive correlation between DAPK2 and LOC101928988 levels in tumoral and adjacent normal tissues. A comparison of gene expression between different grades, stages, and HER2 statuses showed significant findings. ROC curve analysis of DAPK2 and LOC101928988 expression revealed 77% and 72% AUC for BC tissue, respectively.

Conclusions

Overall, our results suggest that alterations in the levels of DAPK2 and LOC101928988 may be involved in tumor initiation and progression in breast cancer. It has also been reported that LOC101928988 probably has a role in regulating DAPK2 expression through interaction with transcription factors.
Active cell proliferation contributes to the enlargement of the nascent nucleus pulposus
Authors: Long Rose G. , Lee Changhee , Tabin Clifford J.
Published: February 2025

Background

The notochord is an embryonic organ involved in forming and patterning the spinal column. The mechanism by which the notochord transforms from a continuous rod to a segmented structure excluded from the vertebrae and residing solely as the nucleus pulposus within the intervertebral disc is understudied. The current model of notochordal segmentation suggests that swelling through formation and maturation of the vertebrate cartilage squeezes the notochord cells from the vertebra.

Results

Analysis of Collagen 10, a marker for hypertrophic differentiation, as well as evaluation of changes in cell density, reveal that the expansion of the vertebral precursor cells occurs after notochord segmentation has already taken place. We find that the bulk of the nucleus pulposus is derived from accelerated proliferation within the nucleus pulposus itself. In a model of cell proliferation, the increased proliferation at the nucleus pulposus importantly contributes to expand the nucleus pulposus area.

Conclusions

Our data is consistent with the hypothesis that notochord cell proliferation contributes to the enlargement of the nucleus pulposus before the vertebra undergo hypertrophy.
Development of the Electrode for the Particle Sampling Using Negative Dielectrophoresis by Additive Synthesis Sine Wave
Authors: Yamaoka Hidehiko , Nagata Kohki , Funahashi Masaya , Yagi Ippei , Uchida Satoshi
Published: February 2025

Currently, no technology has been established to measure the amount of ocean microplastics (MP) less than 5 mm. As a basic study of the quantitative evaluation, the authors proposed measurement method using the attenuation of transmitted light for the amount of microplastic that concentrated by dielectrophoresis. In this study, we report effective collection method of microplastics by combining an electrode structure that generate negative dielectrophoresis and a driving method using additive Synthesis sine wave.
ETS‐NOCV Analysis of σ‐Donation and π‐Backdonation in Complexes of Boron Based Lewis Acids with N2, CO and NH3
Authors: Brinck Tore , Sagan Filip , Mitoraj Mariusz
Published: February 2025

Lewis acids B(SiR3)3 and B(GeR3)3 form anomalously strong complexes with Lewis bases N2 and CO. Intramolecular B‐N/C bonds are generally in the range 1.45‐1.50 Å and shorter than the sum of B and N/C covalent radii. Bonding analyses have showed that the strong bonds are a consequence of a novel σ‐donation and π‐backdonation mechanism, where electrons are donated into an empty sp3‐type orbital on B (LUMO) from the s‐orbitals of N2/CO and electrons are backdonated from the B‐Si/Ge s‐bonds into the p‐type orbitals of N2/CO. Here we have analyzed the complexes between Lewis acids B(SiH3)3 and B(CF3)3 and Lewis bases N2, CO and NH3 using the extended transition state— natural orbitals for chemical valence (ETS‐NOCV) method. Both σ‐donation and π‐backdonation are present in all  complexes, and deformation densities due to the two mechanisms, i.e. NOCV pair densities, are surprisingly similar in character. Energy stabilization due to π‐backdonation is much larger for the complexes of B(SiH3)3 with N2 and CO, and σ‐donation stabilization is also enhanced compared to the corresponding complexes of B(CF3)3. Differential electrostatic potential indicate that the enhanced stabilization of the B(SiH3)3 complexes is largely an effect of reduced charge separation due to the balance between σ‐donation and π‐backdonation.
GATAD2B‐related developmental and epileptic encephalopathy (DEE): Extending the epilepsy phenotype and a literature appraisal
Authors: Scorrano Giovanna , Barcia Giulia , Champ Jérôme , Courtin Thomas , Boddaert Nathalie , Kaminska Anna , Chemaly Nicole , Nabbout Rima
Published: February 2025

Heterozygous pathogenic variants in GATAD2B gene have been related to the GATAD2B‐associated neurodevelopmental disorders (GAND) characterized by neurodevelopmental delay with predominant language impairment, infantile hypotonia, macrocephaly, ophthalmological abnormalities, and dysmorphic facial features with nonspecific findings on brain magnetic resonance imaging (MRI). Occasionally, affected individuals exhibit drug responsive epilepsy, psychiatric disorders, and other extra‐neurological comorbidities. We report a patient carrying a de novo heterozygous missense variant in GATAD2B gene. She presents a developmental and epileptic encephalopathy (DEE) with drug‐resistant atypical absences. An extensive review of the literature did not show any similar phenotype. Our report broadens the electroclinical spectrum related to GATAD2B pathogenic variants and supports the inclusion of this monogenic etiology among the genetic causes of epilepsy with drug‐resistant atypical absences, a group with few known genetic etiologies.

Plain Language Summary

We describe a patient with drug‐resistant atypical absences caused by a pathogenic variant in the GATAD2B gene. Mutations in the GATAD2B gene should be considered among the rare monogenic causes of atypical absences.
Landscape Archaeology of the Chuchuwayha Sacred Site (British Colombia, Canada)
Authors: Delannoy Jean‐Jacques , Quiles Anita , Jacquet Julien , Allison Mike , Braucher Régis , Léanni Laetitia , Malet Emmanuel , Ash Jeremy , Berthet Johan , Clyburn Angela , Delannoy Yago , Geneste Jean‐Michel , Gould Brenda , Harris Megan , Rowley Susan
Published: February 2025

New research is being conducted at the Chuchuwayha sacred site (British Columbia, Canada) at the request of the Upper Similkameen Indian Band, who want to pass on the site's history to future generations. The project's aims were to determine when this site in the glacial Similkameen Valley became accessible to human communities, to reconstruct the formation of the surrounding landscape, and to describe the rock shelter's evolution during the period of human frequentation (rock art). To this end, we combined geomorphological, archaeometric, and geochemical (cosmogenic dating) data to construct a robust chronological framework for the site's evolution and human occupations. Results showed that the Similkameen Valley became ice‐free 18,000 years ago, that the site's morphology was shaped by postglacial processes, and that its general topography had formed around 7000 years ago. The site's morphology—a rock shelter behind a mound of rockfall boulders—created a trap for eolian and autochthonous sediments, which have preserved a record of human occupations. Our multidisciplinary approach also enabled us to determine age ranges for the shelter's paintings, to draw up a new time frame for human occupations of the site, which lies on a traditional Syilx trail, and to relate these occupations to changes in the surrounding landscape.
Geospatial Assessment and Mapping Landslide Susceptibility for the Garo Hills Division, Meghalaya, India
Authors: Badavath Naveen , Sahoo Smrutirekha
Published: February 2025

Creating accurate and effective Landslide Susceptibility (LS) maps can aid disaster prevention and mitigation efforts and provide sufficient public safety. The primary aim of this study is to develop an LS map for the Garo Hills region in Meghalaya, India, using the weight of evidence (WoE), frequency ratio (FR), and Shannon entropy (SE) methods. A comprehensive landslide inventory catalogued 98 events from 2000 to 2023 for the analysis, and nine key geographical and environmental parameters were prepared. Conducted multicollinearity and correlation analysis to identify and mitigate collinearity issues between factors. The model's performance was analysed through the area under the curve (AUC) value of receiver operating characteristic (ROC) curves and three recent landslides. The results showed that FR method achieved the highest accuracy, with successive rate curve (SRC) AUC and predictive rate curve (PRC) AUC values of 0.860 and 0.940, respectively, and classified susceptibility at three sites as high, moderate, and low. The WoE method effectively identified three landslides site in high and very high susceptibility zones, achieving SRC AUC and PRC AUC values of 0.844 and 0.915, respectively. The SE method showed robust performance in predicting landslide‐prone areas, with PRC AUC comparable to other methods (0.913), though its SRC AUC (0.771) was lower. Developed maps revealed that high and very high susceptibility zones account for approximately 10% and 3% of the study area, predominantly near roads, steep slopes, and higher elevations. The information in this study is valuable for civilians and the government authorities involved in hazard monitoring and management.
Intraoperative Low‐Dose Glucocorticoids in Surgical Patients With Abdominal Sepsis: A Multicenter Retrospective Cohort Study
Authors: Tao Tianzhu , Shi Yue , Ye Xiaofei , Mi Weidong , Lou Jingsheng
Published: February 2025

Background and Aims

Abdominal sepsis refers to a severe and potentially life‐threatening condition characterized by the presence of infection, inflammation, and tissue damage within the abdominal cavity. Glucocorticoids (GCs) play an important role in regulation of the host immune and inflammation responses involved in sepsis and surgery. This study aimed to investigate the potential impact of intraoperative GCs administration on the clinical outcome of surgical patients with abdominal sepsis.

Methods

This retrospective cohort study included a 1:1 propensity score–matched cohort of surgical patients afflicted with abdominal sepsis at two medical centers from January 2008 to December 2022. Patients were classified into low‐GCs, high‐GCs, and non‐GCs groups according to the dosage of steroids used intraoperatively, and in‐hospital mortality was designated as the primary outcome.

Results

This study included a total of 476 patients, with 217 in the non‐GCs group, 213 in the low‐GCs group, and 46 in the high‐GCs group. The overall in‐hospital mortality rate was 7.56%. After propensity score matching (PSM), there were 168 cases in both the low‐GCs group and the non‐GCs group, with no significant differences observed between the groups regarding mortality rate, length of hospital‐stay, and duration of intensive care unit (ICU) stay. In patients with septic shock, the use of low‐dose GCs increased the urine output and decreased the requirements for vasopressors on the first postoperative day, however, it had no impact on the in‐hospital mortality or ICU stay. Moreover, prophylactic use of GCs during anesthesia induction did not decrease the incidence of intraoperative hypotension or necessity of vasopressors use.

Conclusion

Intraoperative administration of low‐dose GCs demonstrates a transient improvement in hemodynamics of patients with septic shock, however, it did not lead to improved clinical outcomes. Further research remains necessary to elucidate the optimal perioperative dosing strategy.
Mapping Normative Muscle Health Metrics Across the Aging Continuum: A Multinational Study Pooling Data From Eight Cohorts in Japan, Malaysia and Taiwan
Authors: Chen Liang‐Kung , Meng Lin‐Chieh , Peng Li‐Ning , Lee Wei‐Ju , Zhang Shu , Nishita Yukiko , Otsuka Rei , Yamada Minoru , Pan Wen‐Harn , Kamaruzzaman Shahrul Bahyah , Woo Jean , Hsiao Fei‐Yuan , Arai Hidenori
Published: February 2025

Background

The vigour of our musculature wanes as the years advance, and prognosticating the concomitant trajectories throughout the course of life assumes paramount importance for judicious and timely interventions. In the present study, we aimed to establish age‐ and sex‐specific reference centiles for multiple muscle health metrics and reveal the distributions of these metrics throughout the aging process in the Asian population.

Methods

By using cross‐sectional pooled data of community dwellers aged 20 years or older in eight cohorts from Taiwan, Japan and Malaysia, normative values for muscle health metrics (calf circumference (cm), relative appendicular skeletal muscle (RASM) (kilogram per square metre), body mass index (BMI)–adjusted appendicular skeletal muscle mass (kilogram/(kilogram per square metre)), handgrip strength (kilogram), five‐time chair stand (seconds) and gait speed (metre per second)) in men and women, categorized by age groups, are calculated. The mean values, along with the 5th, 25th, 50th, 75th and 95th percentiles of these muscle health metrics, are also delineated for both sexes.

Results

Among 34 265 (16 164 men, 18 101 women) participants from eight cohorts, calf circumference declined in age groups from 60 years onward. RASM values declined from the 50s in men but were stable in women until the 80s. ASM/BMI values showed declines in older age groups for both sexes. Handgrip strength declined similarly from 40 years of age in both sexes. Five‐time chair stand performance declined from the 30s. Gait speed peaked at 1.6 m/s in men in their 50s and then declined, while it declined in women in their 60s. The inflection points for decline differed by metric and sex. The 20th percentile cutoffs for individuals aged 65–69 years were as follows: calf circumference, 33.0 cm (men) and 31.5 cm (women); RASM, 7.0 kg/m2 (men) and 5.5 kg/m2 (women); ASM/BMI, 0.78 kg/(kg/m2) (men) and 0.56 kg/(kg/m2) (women); handgrip strength, 30.4 kg (men) and 18.1 kg (women); five‐time chair stand, 9.4 s (men) and 10.0 s (women); and gait speed, 0.9 m/s (both). Those in the fifth percentile of all muscle health metrics faced earlier declines than their 95th percentile counterparts did, highlighting the critical roles in identifying these high‐risk groups.

Conclusion

The pooled analysis of eight Asian cohorts clearly outlined the age‐related changes in various muscle health metrics, with the inflection point of accelerated decline showing age‐ and sex‐specific characteristics. Defining trajectories of muscle health metrics across life stages facilitates timely interventions to mitigate age‐related risks and promote healthy longevity.
SIRT6 Ameliorates Cancer Cachexia–Associated Adipose Wasting by Suppressing TNFR2 Signalling in Mice
Authors: Xu Kang , Wang Yida , Wang Fang , Guo Yannan , Ren Yu , Low Vivien , Cho Sungyun , Liu Qingfei , Qiu Ying , Li Xue , Yu Kang , Li Zhongchi , Wang Zhao
Published: February 2025

Background

Cachexia is a wasting syndrome associated with imbalanced energy metabolism and loss of adipose and muscle tissues and contributes to morbidity and mortality in ageing as well as in patients with severe chronic diseases, including cancer. At present, there are no treatments addressing cachexia that have reached validation to be used in the clinic. In this study, we investigate the protective role of SIRT6, an important regulator of energy homeostasis and health preservation, against Lewis lung carcinoma (LLC)–induced cachexia.

Methods

SIRT6 levels of serum from gastric cancer patients (n = 22, 65.27 ± 12.50 years old, 40.9% females) and healthy controls (n = 22, 63.50 ± 10.77 years old, 45.4% females) were measured to evaluate the correlation between circulating SIRT6 levels and cancer cachexia development. Ten‐week‐old SIRT6 transgenic (TG) and wild type (WT) male mice injected with LLC cells (1.5 × 106 per mouse) were used to investigate the protective effects of SIRT6 on cachexia‐associated adipose browning and lipolysis and the underlying mechanisms. We explored the effect of SIRT6 on LLC‐conditioned medium induced lipolysis in mature adipocytes, differentiated from primary mouse embryonic fibroblasts (MEFs). We evaluated the in vitro effect of a SIRT6 activator by treatment of MDL800.

Results

SIRT6 concentrations were significantly higher in non‐cachectic cancer patients (3.41 ± 0.30 ng/mL) compared to cachectic cancer patients (3.20 ± 0.23 ng/mL, p < 0.01), suggesting the negative correlation between SIRT6 level and cachexia in patients with cancer. SIRT6 overexpression significantly ameliorated tumour‐induced wasting and energy expenditure in white adipose tissues (eWAT mass loss: 66% in WT vs. 32% in TG; iWAT mass loss: 69% in WT vs. 40% in TG) through suppression of browning and lipolysis. In LLC‐induced cachexia, tumour necrosis factor‐α receptor 2 (TNFR2) mediated the inhibition of SIRT6 on lipolytic signalling, because the difference in lipolysis between the WT and SIRT6 knockout group was almost eliminated by TNFR2 neutralizing antibody. Increased serum TNFR2 concentration was found in cachectic cancer patients (690.41 pg/mL in non‐cachectic vs. 1166.98 pg/mL in cachectic patients, p < 0.05). A selective SIRT6 pharmaceutical activator, MDL800, could completely reverse LLC‐induced lipolysis in adipocytes.

Conclusion

We found an unexpected beneficial function of SIRT6 in cancer cachexia, demonstrating that increased SIRT6 expression or activity is capable of protecting the host against cachexia‐associated tissue wasting, providing a concept of future therapies for cachexia.
Supervision for genetic counselors: The role of career‐long supervision to develop resilient practitioners
Authors: McEwen Alison , Davys Allyson , Weil Jon
Published: February 2025

Supervision is a professional activity that provides practitioners with opportunities to reflect on, integrate and learn from work experiences, build resilience, and develop and review their professional identity through reflective conversations with a supervisor and/or peers. Supervision involves a contractual agreement between a supervisor and supervisee (practitioner), that recognizes the accountability of the supervision process to professional and organizational standards and protocols. Incorporating supervision into practice for genetic counselors at all career stages provides a way to develop and strengthen competence and practice and support genetic counselor well‐being and client safety. Evidence also suggests that active engagement with effective professional supervision reduces the likelihood of burnout in healthcare workers. Genetic counselors in some parts of the world, including Australia, New Zealand, and the United Kingdom, participate in career‐long supervision as a requirement of certification and registration. As the genetic counseling profession expands and diversifies, individuals and professional societies are encouraged to embed the practice of supervision beyond graduate training, establishing a professional culture that values career‐long facilitated reflection and learning. We propose the establishment of a global genetic counseling supervision community of practice for genetic counselors interested in developing supervision practices and sharing resources.
RNA Interference Targeting Small Heat Shock Protein B8 Failed to Improve Distal Hereditary Motor Neuropathy in the Mouse Model
Authors: Vendredy Leen , De Winter Vicky , Van Lent Jonas , Orije Jasmien , Authier Tatiana Da Silva , Katona Istvan , Asselbergh Bob , Adriaenssens Elias , Weis Joachim , Verhoye Marleen , Timmerman Vincent
Published: February 2025

Background

Missense mutations in the HSPB8 gene, encoding the small heat shock protein B8, cause distal hereditary motor neuropathy (dHMN) or an axonal form of Charcot–Marie–Tooth disease (CMT subtype 2L). Mice expressing mutant Hspb8 (Lys141Asn) mimic the human disease, whereas mice lacking Hspb8 show no overt phenotype. We aimed to design an RNA interference treatment strategy that rescues the mutant HSPB8 neuronal and muscle phenotype in patient‐derived motor neurons and in a knock‐in mouse model of CMT2L/dHMN.

Methods

We optimized RNA interference sequences targeting both human HSPB8 and mouse HspB8 transcripts with the aim to alleviate disease symptoms. We used human induced pluripotent stem cells and the Hspb8 knock‐in mouse model. We designed lenti‐ and adeno‐associated viral vectors that contained the short‐hairpin RNA constructs. We performed expression and microscopy studies, magnetic resonance imaging, behaviour analysis and electrophysiology.

Results

In CMT2L patient‐derived induced pluripotent stem cells differentiated towards motor neurons, reducing the HSPB8 expression with a short‐hairpin RNA (shRNA), directed towards the 3′ untranslated region (3′UTR), ameliorated the morphology and fragmentation of mitochondria. The AAV9‐mediated treatment of the 3′UTR shRNA construct, under neuron‐specific regulation, in Hspb8 knock‐in mice showed inconclusive results towards functional improvement upon expression studies, magnetic resonance imaging and neuropathological findings.

Conclusions

Given the limited beneficial effect of the treatment, the RNA interference–mediated reduction of HSPB8/Hspb8 expression might not be the best therapeutic strategy to treat dHMN/CMT2L, unless a higher viral load and earlier treatment can be applied to the mouse model.
Habitat and connectivity‐based conservation strategies for the vulnerable Lorestan newt (Neurergus kaiseri) in the Zagros Mountains, Iran
Authors: Vaissi Somaye , Mohammadi Alireza
Published: February 2025

The Lorestan newt (Neurergus kaiseri) is a vulnerable amphibian endemic to the Zagros Mountains in Iran. This study aimed to identify core habitats, assess potential dispersal corridors, and evaluate the effectiveness of current conservation efforts. Ensemble species distribution models predicted suitable habitat across the newt's range, with annual precipitation and temperature as the most influential factors. Connectivity simulations revealed critical core habitats, primarily concentrated in the northwestern region, that spanned 2,233.43 km², none of which fell within designated protected areas. Corridor analysis identified viable dispersal pathways between northern and southern populations, but only 2.77% of the corridor network was protected. Roads and dams frequently intersected putative corridors, posing significant fragmentation threats. These results underscore the urgent need for expanded conservation efforts, including the establishment of new protected areas and measures to mitigate habitat fragmentation, to ensure the connectivity and long‐term viability of Lorestan newt populations. Our findings provide valuable insights to guide future conservation strategies for this endangered species.
Deep medial collateral ligament plays a stabilising role under degenerative medial meniscus root tears
Authors: Funchal Luis Fernando Z. , Galibern Leonardo , Ortiz Rafael , Astur Diego C. , Cohen Moises , Roesler Carlos R. , Fancello Eduardo A.
Published: February 2025

Purpose

Several posterior medial meniscal root (PMMR) repair techniques have been developed to restore the load‐bearing function of the meniscus and reduce extrusion. The medial meniscotibial ligament (MMTL) has been shown to play a significant role in meniscal stability. This study evaluates the stabilising function of the MMTL by directly influencing the force exerted on the PMMR during weight‐bearing and valgus motion of the knee. Our aim is to investigate whether loss of MMTL integrity is a determining factor in PMMR subluxation.

Methods

Using a 3D model of the knee with parameters from experimental studies, compressive and valgus loading scenarios were simulated using the finite element method to analyse the mechanical response of different knee structures. To investigate the correlation between the integrity of the MMTL and the force acting on the PMMR, different degrees and types of injuries to both structures were modelled for comparison with the healthy joint, providing insights into their importance in preventing or correcting extrusion.

Results

During compressive loading, tears in the MMTL and PMMR result in a 5.8% and 30.9% increase in meniscal extrusion, respectively, while a combined injury results in a 43.9% increase, indicating that the MMTL provides a secondary constraint against extrusion. Moreover, the importance of the MMTL in restraining extrusion becomes more pronounced as the PMMR weakens, as is typical in degenerative tears. Finally, during valgus motion, the MMTL prevents separation of the meniscus from the tibial plateau and reduces strain/stress on the PMMR.

Conclusion

The integrity of the MMTL plays a crucial role in reducing meniscal extrusion and PMMR overload, particularly when the root is affected by degenerative tears. Therefore, surgical repair of the MMTL can improve meniscal function, potentially reducing the risk of osteoarthritis and should be considered as a better treatment strategy for PMMR tears.

Level of Evidence

Level III.
AI‐Powered Laryngoscopy: Exploring the Future With Google Gemini
Authors: Setzen Sean A. , Andreadis Katerina , Elemento Olivier , Rameau Anaïs
Published: February 2025

Foundation models (FMs) are general‐purpose artificial intelligence (AI) neural networks trained on massive datasets, including code, text, audio, images, and video, to handle myriad tasks from generating texts to analyzing images or composing music. We evaluated Google Gemini 1.5 Pro, currently the largest token context window multimodal FM and best‐performing commercial model for video analysis, for interpreting laryngoscopy frames and videos from Google Images and YouTube. Gemini recognized the procedure as laryngoscopy in 87/88 frames (98.9%) and in 15/15 video‐laryngoscopies (100%), accurately diagnosed a pathology in 55/88 frames (62.5%) and 3/15 videos (20.0%), identified lesion sides in 58/88 frames (65.9%) and 6/15 videos (40%) and narrated two operative video‐laryngoscopies without fine‐tuning. Findings suggest that Gemini 1.5 Pro shows significant potential for analyzing laryngoscopy, demonstrating the potential for FMs as clinical decision support tools in complex expert tasks in otolaryngology.

Level of Evidence

3
Improved Oxidation Stability of 1,3‐Diketone Superlubricity Fluid Using a Butylated Hydroxytoluene Additive
Authors: Yang Yan , Chen Jingfu , Amann Tobias , Yuan Chengqing , Li Ke
Published: February 2025

As an oil‐based superlubricity material on steel surfaces, 1,3‐diketone fluid is promising for the friction reduction of mechanical devices. However, the unsaturation of its molecular structure would potentially cause the oxidation problem in industrial applications. In this study, the oxidation mechanism of diketone fluid 1‐(4‐ethyl phenyl) nonane‐1,3‐dione (EPND) was discovered through the accelerated oxidation experiment in an oven. By doping butylated hydroxytoluene (BHT) anti‐oxidation additive at an optimal concentration of 0.5%, both the oxidation onset temperature (OOT) and oxidation induction time (OIT) of EPND could be enhanced to a comparable level of 4121 commercial oil, which is a fully‐formulated lubricant with a similar viscosity to EPND. Moreover, the friction test verified that the incorporated BHT additive induced negligible influence on the superlubricity performance of EPND. The result of this study is helpful for improving the weakness of the diketone superlubricity system and promotes a further step in its practical applications.
The Effect of Vaginal Er:YAG Laser Therapy on Pelvic Floor Symptoms in Women With Stress Urinary Incontinence: A Single‐Center Cohort Study
Authors: Lia Massimiliano , Pilát Pavel , Weydandt Laura , Baessler Kaven , Kempe Tom , Aktas Bahriye
Published: February 2025

Objectives

To examine the effect of vaginal erbium:yttrium‐aluminum‐garnet (Er:YAG) laser therapy on pelvic floor symptoms in women with stress urinary incontinence (SUI).

Methods

This was a prospective, single‐arm interventional study applying three Er:YAG laser treatments to patients with SUI. The German version of the validated Australian Pelvic Floor Questionnaire was used to quantify pelvic floor symptoms (bladder function, bowel function, sexual function, pelvic organ prolapse) over different time points (baseline, posttreatment, 3 months, and 6 months after treatment). Subgroups were compared to examine which factors influenced symptom development after the treatment.

Results

A total of 50 women received three Er:YAG laser treatments and had their symptoms evaluated at all time points of the study. All symptom complex scores, especially bladder function and sexual function, showed statistically significant improvements lasting for the whole study period. However, score improvements of bowel function and prolapse symptoms were likely not clinically meaningful, as they were below the minimal important difference (MID) of this questionnaire. Moreover, sexual function scores improved less when women additionally had urgency symptoms (i.e., mixed urinary incontinence [MUI]; p = 0.036).

Conclusion

Vaginal Er:YAG laser therapy has the potential to improve pelvic floor symptoms linked to bladder function and sexual function in women with SUI. However, the positive effect on sexual function was lower if the women had MUI.
Impact of Minor Changes in Molybdenum Content on the Localized Corrosion Resistance of Austenitic Stainless Steels
Authors: Reyad Ahmed , Hornus Edgar , Bhatti Farid , Parapurath Shahid , Sapanathan Thaneshan , Iannuzzi Mariano
Published: February 2025

As an alloying element, molybdenum has a positive impact on the localized corrosion resistance of stainless steels and Ni‐based alloys. Nevertheless, the impact of minor changes from 0.5 to 1.0 wt% within the composition boundaries of SS316L on localized corrosion resistance is poorly understood. This study investigates the influence of these variations on the localized corrosion resistance of SS316L. Using the potentiodynamic–galvanostatic–potentiodynamic (PD–GS–PD) technique, the crevice corrosion repassivation potential (ER,CREV) was measured in deaerated natural seawater at various temperatures for three stainless steel grades with differing Mo contents. The ER,CREV of SS316‐2.5Mo increased by approximately 125 mV at 10°C, 139 mV at 20°C, and 218 mV at 35°C when compared to SS316‐2Mo. Microstructure analysis after PD–GS–PD revealed Mo‐enriched precipitates for both SS316‐2.5Mo and SS317‐3Mo. Potentiodynamic polarization test was conducted in pit/crevice‐like conditions, showed improved corrosion resistance in SS316‐2.5Mo, as indicated by higher breakdown and Flade potentials, a wider passive range, particularly in 1 M [Cl−] (pH = 0).
Multi‐Stimulus Responsive Nonconventional Fluorescent Supramolecular Polymeric Material
Authors: Hao Wentao , Ke Chenchen , Pan Xianxiang , Qi Tengfei , Wang Wenping , Li Wenjuan , Yang Wen
Published: February 2025

Fluorescent supramolecular materials have attracted a lot of attention over the past few decades. However, those can respond to multiple stimuli are not often reported, especially for the nonconventional fluorescent materials. Here, a supramolecular material is reported that can respond to temperature/electrical heating, humidity, volatile acids/organic amines, and mechanical strain. This material is prepared by physical mixing oligomeric polyethyleneimine (o‐PEI) and oligomeric polyacrylic acid (o‐PAA). Although they are almost non‐fluorescent, their combination produces bright fluorescence, and the emission bands shift to longer wavelengths as the amount of o‐PAA increases. Calculations based on Density Functional Theory (DFT) show that there are strong noncovalent interactions between o‐PEI and o‐PAA, resulting in through‐space conjugation and cluster‐triggered emission. By studying the relationship between emission intensity, temperature, and molecular motion, the dependence of emission intensity on relaxation time is established, which will provide insight into the luminescence origin of nonconventional fluorescent materials. In addition, this material shows good self‐healing ability. The luminescence, responsiveness and self‐reparability are all related to the strong but reversible noncovalent bonds that link the o‐PEI and o‐PAA. This work not only highlights the value of supramolecular polymers, but also enriches the research of nonconventional fluorescent materials.
Heat Build‐Up of Rubber in Different Deformation Modes and Its Correlation to Viscoelasticity
Authors: Nie Shouliang , Huang Wei , Ren Pengjie , Wang Xiaorong
Published: February 2025

Heat build‐up (HBU) under deformation is a critical characteristic of rubber materials, and it significantly influences the performance and service safety of final products. In addition, the deformation modes of materials can vary considerably depending on the product and working conditions, resulting in a complex and sometimes unpredictable correlation between HBU and the viscoelasticity of materials. In this study, strain‐ and stress‐controlled HBU experiments on rubber composites are conducted using a dynamic mechanical analyzer (DMA) equipped with a sample temperature measuring unit. During the HBU tests, dynamic mechanical properties are monitored simultaneously with HBU, ensuring a direct correlation between viscoelasticity and heat generation. The energy density of dissipation, Wdiss in the stress–strain hysteresis loop, is considered to be the source of heat generation and can be expressed through various rheological parameters. It is found that, in strain‐controlled mode, the HBU of tested materials correlates linearly with the loss modulus, . In contrast, in stress‐controlled mode, the HBU correlates linearly with the combined formats of rheological parameters, such as . These results suggest a new guideline for applying viscoelastic parameters, or their combinations, as evaluation indicators for the performance of rubber materials based on their working conditions.
Unmasking a Recessive Allele by a Rare Interstitial Deletion at 10q26.13q26.2: Prenatal Diagnosis of MMP21 ‐Related Disorder and Further Refine INSYN2A Involvement in the Postnatal Cognitive Phenotype
Authors: Su Jiasun , Zhang Shujie , Li Wei , Wei Yuan , Lin Fei , Zhou Chaofan , Tang Xianglian , Lan Yueyun , Huang Minpan , Zhang Qiang , Yi Shang , Yang Qi , Yi Sheng , Zhou Xunzhao , Qin Zailong , Huang Peng
Published: February 2025

Background

The 10q26 microdeletion syndrome (OMIM #609625) is a distinct genomic disorder characterized by a spectrum of clinical features including craniofacial anomalies, developmental delay (DD)/intellectual disability (ID), hypotonia, cardiovascular, and urogenital malformations. Despite the identification of critical regions within 10q26 linked to the syndrome's phenotype, the specific genes responsible for the associated facial characteristics, microcephaly, cognitive issues, and growth deficiencies remain elusive. Interstitial deletions at 10q25.3‐q26.3 are rare, and their contributions to 10q26 microdeletion syndrome remain unknown.

Methods

We conducted trio‐whole‐exome sequencing (WES) on a fetus presenting with ventricular septal defect (VSD), aortic span, intrauterine growth retardation (IUGR), and microcephaly. Variant classification was assessed according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, and the causative gene associated with cognitive phenotype was refined by means of smallest regions of overlap (SRO).

Results

A homozygous variant c.1544A>G (p.Tyr515Cys) in MMP21 and a large deletion at 10q26.13‐q26.2 which unmasked the homozygous mutation were identified in the proband. The maternally inherited 10q26.13q26.2 deletion was classified as likely pathogenic, while the variant c.1544A>G was of uncertain significance (VUS) based on ACMG/AMP criteria. A critical interval of approximately ~500 kb implicating the involving genes DOCK1 and INSYN2A (inhibitory synaptic factor 2A) in the cognitive phenotype of 10q26 microdeletion syndrome was refined.

Conclusion

This study introduces a recessive MMP21 mutation unmasked by a rare 10q26.13q26.2 deletion via WES in a Chinese fetus with congenital heart disease (CHD), IUGR, and microcephaly. We further refine INSYN2A as a potential candidate gene for cognitive phenotype in 10q26.1‐q26.3 region. Our study also highlights the utility of WES for its advantage in simultaneously analyzing both single nucleotide variants (SNVs) and copy number variants (CNVs) and provide a reference for prenatal diagnosis and genetic counseling in patients with similar conditions.
Suicide: The Experiences of Attempters in the Greater Accra Region of Ghana
Authors: Buertey Abigail Ansere
Published: February 2025

Suicide is a major public health concern that has negatively impacted people worldwide socioeconomically, physically, and psychologically. Every instance is a heart‐breaking loss that deeply impacts families, communities and nations, leaving lasting repercussions for those left behind. The aim of the study was to explore precipitating factors of people who experienced a suicide attempt. A qualitative descriptive exploratory design was used with the help of a semi‐structured interview guide to collect data from thirteen (13) suicide attempters' with ages between 20 and 48 years. The data were transcribed verbatim after it had been audio recorded digitally. The data were analyzed using thematic analysis with MAXQDA 20. Information gathered yielded two major themes and six subthemes as the precipitating factors for suicide attempt. The two main themes were (1) Social/family issues, with its subthemes; mistrust, wasted resources and parental pressure (2) Psychological issues with the subthemes; Childhood experiences, emotional breakdown and difficult life pursuits. The study showed that suicide is a very complex problem in every society and there is general ignorance about the triggers, signs and appropriate help seeking strategies. It is therefore vital to create massive public awareness on suicide attempt triggers and symptoms through health education to help save lives.
Boosting 2D brain image registration via priors from large model
Authors: Lin Hao , Song Yonghong
Published: February 2025

Background

Deformable medical image registration aims to align image pairs with local differences, improving the accuracy of medical analyses and assisting various diagnostic scenarios.

Purpose

We aim to overcome these challenges: Deep learning‐based registration approaches have greatly enhanced registration speed and accuracy by continuously improving registration networks and processes. However, the lack of extensive medical datasets limits the complexity of registration models. Optimizing registration networks within a fixed dataset often leads to overfitting, hindering further accuracy improvements and reducing generalization capabilities.

Methods

We explore the application of the foundational model DINOv2 to registration tasks, leveraging its prior knowledge to support learning‐based unsupervised registration networks and overcome network bottlenecks to improve accuracy. We investigate three modes of DINOv2‐assisted registration, including direct registration architecture, enhanced architecture, and refined architecture. Additionally, we study the applicability of three feature aggregation methods—convolutional interaction, direct fusion, and cross‐attention—within the proposed DINOv2‐based registration frameworks.

Results

We conducted extensive experiments on the IXI and OASIS public datasets, demonstrating that the enhanced and refined architectures notably improve registration accuracy, reduce data dependency, and maintain strong generalization capabilities.

Conclusion

This study offers novel approaches for applying foundational models to deformable image registration tasks.