bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution and development of railway passenger transportation clearing method in China
Authors: Zhou Yin , Fang Wei , Xu Yan , Wang Huaixiang , Liu Lu
Published: January 2025

Purpose

As an important part of the management of railway passenger transport, the rationality and effectiveness of the clearing method of railway passenger transport are directly related to the operating efficiency and service quality of railway passenger transport enterprises. This paper aims to comprehensively and deeply discuss the evolution and development process of China’s railway passenger transport clearing method, analyze its characteristics and influences in each stage, identify the main factors affecting its evolution and development and then put forward thoughts on improving the future development of the clearing method.

Design/methodology/approach

Through a detailed review of the railway passenger transport clearing methods from the planned economy period to the reform and opening up period and into the new century, the basis, mode, subject and object of clearing in different development stages are systematically compared.

Findings

It comprehensively reveals the evolution of the clearing method, sorted out the characteristics and changes of the clearing method at each stage and the adaptability to the development of railway passenger transport at that time. The characteristics of the development of clearing measures for railway passenger transport in different stages and their far-reaching influence on railway passenger transport business are deeply analyzed.

Originality/value

This paper summarized the factors influencing the development of China’s railway passenger transportation clearing approach evolution, including the simplified rules of clearing, enhanced the market adaptability, establishing and perfecting the incentive mechanism, strengthening the construction of informatization, etc. This paper puts forward the ways to improve the railway passenger transportation clearing future development thinking.
Baclofen modulates the immune response after spinal cord injury with locomotor benefits
Authors: de Sousa Nídia , Correia‐Silva Ariana , Pinho Andreia G. , Vidinha‐Mira André , Cainé Laura , Lima Marta F. , Santos Diogo J. , Cibrão Jorge R. , Campos Jonas , Cavaleiro Helena , Pinho Tiffany S. , Afonso João L. , Sampaio‐Marques Belém , Monteiro Susana , Silva Nuno A. , Barreiro‐Iglesias Antón , Salgado António J.
Published: January 2025

Background and Purpose

Spinal cord injury (SCI) is a neurological condition that affects motor and sensory functions below the injury site. The consequences of SCI are devastating for the patients, and although significant efforts have been done in the last years, there is no effective therapy. Baclofen has emerged in the last few years as an interesting drug in the SCI field. Already used in the SCI clinical setting to control spasticity, baclofen has shown important impact on SCI recovery in animal models, such as lampreys and mice.

Experimental Approach and Key Results

Herein, we proposed to go deeper into baclofen’s mechanism of action and to study its role on the modulation of the immune response after SCI, a major process associated with the severeness of the lesion. Using a SCI compression mice model, we confirmed that baclofen leads to higher locomotor performance, but only at 1 mg·kg−1 and not in higher concentrations, as 5 mg·kg−1. Moreover, we found that baclofen at 1 mg·kg−1 can strongly modulate the immune response after SCI at local, systemic and peripheric levels. This is interesting and intriguingly at the same time, since now, additional studies should be performed to understand if the modulation of the immune response is the responsible for the locomotor outcomes observed on Baclofen treated animals.

Conclusion and Implications

Our findings showed, for the first time, that baclofen can modulate the immune response after SCI, becoming a relevant drug in the field of the immunomodulators.
Toll‐like receptor 4 deficiency ameliorates experimental ileitis and enteric neuropathy: Involvement of nitrergic and 5‐hydroxytryptaminergic neurotransmission
Authors: Faggin Sofia , Cerantola Silvia , Caputi Valentina , Tietto Angela , Stocco Elena , Bosi Annalisa , Ponti Alessandra , Bertazzo Antonella , Macchi Veronica , Porzionato Andrea , Savarino Edoardo V. , Giaroni Cristina , Giron Maria Cecilia
Published: January 2025

Background and Purpose

Inflammatory bowel disease (IBD) patients display genetic polymorphisms in toll‐like receptor 4 (TLR4) genes, contributing to dysregulate enteric nervous system (ENS) circuits with increased levels of 5‐HT and alteration of the neuroimmune crosstalk. In this study, we investigated the impact of TLR4 signalling on mouse ENS dysfunction caused by dextran sulphate sodium (DSS)‐induced ileitis.

Experimental Approach

Male C57BL/6J (wild‐type [WT]) and TLR4−/− mice (10 ± 2 weeks old) received 2% DSS in drinking water for 5 days and then were switched to 3‐day regular drinking water. Histological analysis and proinflammatory cytokine mRNA levels were assessed in ileal samples. Gut motility was evaluated by changes in transit of a fluorescent‐labelled marker and isometric neuromuscular responses of ileal full‐thickness segments to receptor and non‐receptor‐mediated stimuli. Alterations in ENS architecture were assessed by confocal immunohistochemistry in longitudinal muscle–myenteric plexus whole‐mount preparations.

Key Results

In WT mice, DSS treatment caused delayed gastrointestinal transit, ileal myenteric neurodegeneration, reactive gliosis and release of proinflammatory cytokines. Enhanced cholinergic and tachykinergic excitatory tone, increased inducible nitric oxide synthase (iNOS)‐mediated relaxation, and changes in 5‐HT2A and 5‐HT3 receptor‐mediated responses were observed during ileitis in WT mice. TLR4 deficiency reversed most of the functional and morphological abnormalities.

Conclusion and Implications

Our results demonstrate that TLR4 activity influences the severity of ileitis, neuroglial plasticity, gut motility, and nitrergic and 5‐HTergic neurotransmissions. The neuroimmune interaction between TLR4 and 5‐HT observed in our study appears to be a potential pharmacological target to treat ENS dysfunction implicated in IBD onset/progression.
A Homozygous Variant in HSD17B1 Identified in Women With Poor Ovarian Response
Authors: Ren Jingyi , Ouyang Yan , Wang Shuangyao , Gong Fei , Lu Guangxiu , Lin Ge , Guo Jing
Published: January 2025

An increasing number of patients utilizing in vitro fertilization (IVF) and assisted reproductive technology (ART) are characterized as impaired or poor ovarian responders (PORs). Owing to its unclear molecular etiology, the management of patients with age‐related ovarian characteristics remains a controversial and complex clinical concern. Therefore, it is important to identify and understand the etiological causes behind POR to develop more effective and efficient management strategies for these patients. In this study, we report a homozygous HSD17B1 (accession number: NM_000413.4) variant (c.718‐1G>C) in a patient with POR from a consanguineous family. The proband, a 33‐years‐old woman, exhibited poor ovarian reserve prestimulation parameters (antral follicle count < 5; anti‐Müllerian hormone = 0.386 ng/mL), resulting in the classification of this patient as patient oriented strategies encompassing individualized oocyte number (POSEIDON) group three according to the POSEIDON criteria. Additionally, this patient displayed impaired estradiol production and reduced 17‐ketosteroids secretion and multiple ovarian cysts, which differed from previously reported POR cases. Overall, our findings provide valuable insights for researchers and clinicians into the relationships between the phenotype and genotype of POR and the HSD17B1 gene.
UV photoluminescence in lycaenid butterfly larvae and implications for nocturnal monitoring
Authors: Tilley Gareth J. , Stewart Alan J. A.
Published: January 2025

Nocturnal ultraviolet (UV) flashlight surveys offer a valuable method for investigating butterfly species with cryptic larvae. Focusing on the Lycaenidae, we address three fundamental questions to inform the design of such surveys and the wider significance of this phenomenon. Do the larvae of all species photoluminesce? Which larval instars photoluminesce and how can this information be used to help determine the optimum timeframe in which to search for larvae in the field? Is the level of photoluminescence in different species affected by the UV wavelength used?

Thirteen species of lycaenid butterfly across three subfamilies were tested for photoluminescence in response to UV flashlight. Eight species photoluminesced strongly under 365 nm compared to six under 385–395‐nm UV light. Five species exhibited no photoluminescent response to either wavelength. Neither ova nor pupae of any species tested photoluminesced.

Photoluminescence in Satyrium pruni (Black Hairstreak) larvae increased with larval stage under controlled laboratory conditions. A similar effect was found in other species of Theclinae but was initiated at different stages.

When monitoring lycaenid larvae, it is recommended that a 365 nm flashlight is trialled first and researchers consider when photoluminesce properties develop in larvae when assessing the optimum timeframe for conducting surveys.
Real options investments: Lessons from the US shale gas industry
Authors: Elbakidze Levan , Mugabe Douglas , Zaynutdinova Gulnara R.
Published: January 2025

Using detailed project‐level investment data from the U.S. upstream natural gas industry, we examine the effect of the unexercised real options on individual firms’ real options investments. Drilling an unconventional well is a real options investment that is exercised by fracturing and completing the drilled well at an opportune time. We find a small negative but statistically significant effect of the number of unexercised options on real options investments. There is also a significant difference in the effect of unexercised real options on real options investment decisions of publicly traded and privately held firms.
Hepatitis C Treatment With Generic Sofosbuvir‐Based Regimens in Patients Undergoing Hemodialysis
Authors: Afredj Nawal , Boumendjel Mustapha , Mahiou Hassen , Drir Othmane , Cheikh Ibtissem Ouled , Belimi Hibatallah , Kerbouche Rafik , Guessab Nawal , Zaidi Arezki , Boutra Fouad , Nakmouche M'hamed , Debzi Nabil
Published: January 2025

Objectives

To assess the efficacy and safety of locally manufactured generic sofosbuvir‐based direct‐acting antivirals in the treatment of Hepatitis C virus (HCV) infected patients on maintenance hemodialysis.

Patients and Methods

We have conducted a retrospective multicenter study including patients on maintenance hemodialysis, treated with sofosbuvir‐based regimens between 01/01/2017 and 09/30/2021. Patients were treated for 12 or 24 weeks, with sofosbuvir 400 mg + ledipasvir 90 mg 3 times/week, or sofosbuvir 3 times/week + daclatasvir 60 mg/d, or sofosbuvir + daclatasvir in coformulation, 3 times/week. Sustained virological response was defined as a negative HCV RNA test 12 weeks after treatment. The occurrence of serious adverse events during treatment defines intolerance to treatment. Statistical analysis was performed using SPSS software (version 25).

Results

A total of 120 patients were treated; the mean age was 50 ± 14.17 years [18–78], 50% were men. Twenty‐two patients (n = 22; 18.3%) were previously treated with pegylated Interferon. Genotype 1 was predominant (n = 68; 82%). Most of the patients (n = 53; 44.2%) had no significant fibrosis, and 24 (20%) had cirrhosis. The SVR rate was 93.3% (CI 95% [88.8; 97.8]) (n = 112), the serious adverse events rate was 10.8% (CI 95% [0.054–0.166]) (n = 13), including 2 deaths unrelated to direct‐acting antivirals. Early treatment discontinuation occurred in 5.8% (n = 7), and a relapse in 0.8% (n = 1). On multivariate analysis, risk factors for serious adverse events included advanced liver fibrosis, thrombocytopenia, hypoalbuminemia, high bilirubin level, and pre‐treatment status.

Conclusion

Locally manufactured generic sofosbuvir‐based regimens are safe and effective in maintenance hemodialysis patients. However, they should be closely monitored to manage comorbidities and complications during treatment.
Consumer Decision‐Making Processes Regarding Healthy Food Choices: A Systematic Literature Review and Future Research Agenda
Authors: Shah Priya , Mahajan Harleen , Sompura Nidhi H. , Sunil Anitha , Naldurgakar Rucha
Published: January 2025

This study systematically reviews the literature on consumer perceptions of healthy food choices, employing the ADO (Antecedents, Decisions, Outcomes) framework to analyze 118 peer‐reviewed articles. The research identifies significant inconsistencies in consumer definitions and understanding, influenced by evolving scientific knowledge and diverse information cues. These challenges highlight critical research gaps and underscore the need for strategic marketing interventions and consumer segmentation based on these evolving perceptions. The review proposes a conceptual framework that elucidates the complex interplay between antecedents, decisions, and outcomes in dietary behaviors. The findings aim to empower consumers with evidence‐based strategies for informed dietary choices, contributing to improved public health outcomes. By consolidating fragmented research, this study offers valuable insights for practitioners and policymakers to develop effective marketing strategies and public health initiatives that encourage healthier eating habits.
Enhancing oocyte competence in patients with polycystic ovarian syndrome: A microfluidic study on the effects of follicular fluid meiosis‐activating sterol in in vitro oocyte maturation
Authors: Torkashvand Hossein , Shabani Ronak , Artimani Tayebe , Pilehvari Shamim , Moghimi Mahdi , Torkashvand Leila , Ashrafi Mahnaz , Mehdizadeh Mehdi
Published: January 2025

Objective

To evaluate the efficacy of a microfluidic culture system supplemented with follicular fluid meiosis‐activating sterol (FF‐MAS) on the maturation of immature oocytes in patients with polycystic ovarian syndrome (PCOS).

Methods

A total of 438 germinal vesicle oocytes from 163 PCOS patients were included. Oocytes were divided into five groups: (1) cultured in static drops without FF‐MAS, (2) cultured in static drops with FF‐MAS, (3) cultured in a microfluidic device without FF‐MAS, (4) cultured in a microfluidic device with FF‐MAS for the first 2 h, and (5) cultured in a microfluidic device with FF‐MAS for 24 h. Maturation, fertilization, and embryo development rates were assessed, alongside gene expression analysis using quantitative real‐time PCR. Ultrastructural analysis was performed using transmission electron microscopy (TEM).

Results

The maturation rates for oocytes in groups 1 to 5 were 36%, 48%, 42%, 64%, and 65%, respectively, with groups 4 and 5 showing significant increases (p < 0.05). Fertilization rates were higher in groups 4 and 5 (p < 0.05). High‐quality embryo formation rates were significantly higher in groups 3, 4, and 5. Gene expression analysis indicated enhanced expression of BRCA1 and TP53 in the dynamic culture groups. Ultrastructural analysis showed improved mitochondrial integrity and cytoplasmic maturation in the dynamic groups.

Conclusions

The dynamic microfluidic culture system with FF‐MAS supplementation significantly enhances oocyte maturation and embryo quality in PCOS patients by closely mimicking the natural in vivo environment. This approach shows promise for optimizing in vitro oocyte maturation and improving fertility outcomes.
Championing new ideas with consultation
Authors: Mahaney Joshua , Gillier Thomas , Schweitzer Fiona
Published: January 2025

Idea championing is key for implementing new ideas. A few research studies show that inventors use the consultation tactic to champion their new ideas inside organizations—that is, inventors ask others to contribute to their new ideas in the hope of obtaining others' commitment. However, prior research does not indicate why inventors should use consultation and when it is beneficial. This research proposes that consultation enhances psychological ownership, and that psychological ownership increases idea commitment. Additionally, we posit that the extent to which idea receivers contribute and build psychological ownership will vary depending on the format of the new idea. We hypothesize that consultation is beneficial when idea receivers are asked to contribute to low‐elaborated ideas framed in a non‐narrative format, as this type of idea format provides greater opportunities for inputs. In contrast, we argue that idea receivers build less psychological ownership when they are asked to contribute to high‐elaborated ideas and/or ideas framed in a narrative format (e.g., storytelling). An exploratory survey with 204 inventors confirms that the use of consultation for gaining idea commitment is widespread in companies. The survey shows that inventors present their new ideas at varying levels of elaboration and narrative format. Furthermore, three laboratory experiments provide strong support for our predictions. This study extends our understanding of the idea championing process by providing new insights into how consultation best fosters psychological ownership.
Transgene‐free genome editing in poplar
Authors: Hoengenaert Lennart , Anders Chantal , Van Doorsselaere Jan , Vanholme Ruben , Boerjan Wout
Published: January 2025

Precise gene‐editing methods are valuable tools to enhance genetic traits. Gene editing is commonly achieved via stable integration of a gene‐editing cassette in the plant's genome. However, this technique is unfavorable for field applications, especially in vegetatively propagated plants, such as many commercial tree species, where the gene‐editing cassette cannot be segregated away without breaking the genetic constitution of the elite variety.

Here, we describe an efficient method for generating gene‐edited Populus tremula × P. alba (poplar) trees without incorporating foreign DNA into its genome. Using Agrobacterium tumefaciens, we expressed a base‐editing construct targeting CCoAOMT1 along with the ALS genes for positive selection on a chlorsulfuron‐containing medium.

About 50% of the regenerated shoots were derived from transient transformation and were free of T‐DNA. Overall, 7% of the chlorsulfuron‐resistant shoots were T‐DNA free, edited in the CCoAOMT1 gene and nonchimeric.

Long‐read whole‐genome sequencing confirmed the absence of any foreign DNA in the tested gene‐edited lines. Additionally, we evaluated the CodA gene as a negative selection marker to eliminate lines that stably incorporated the T‐DNA into their genome. Although the latter negative selection is not essential for selecting transgene‐free, gene‐edited Populus tremula × P. alba shoots, it may prove valuable for other genotypes or varieties.
The Interaction Between ABA and Sugar Signalling Regulates Stomatal Production in Systemic Leaves by Controlling Sucrose Transport
Authors: Yao Zi‐Meng , Shi Ya‐Na , Zou Ya‐Li , Meng Lai‐Sheng
Published: January 2025

A key feature of stress responses [closely relative to the phytohormone abscisic acid (ABA)] and associated acclimation in plants is the dynamic adjustments and related optimisation of carbohydrate content between sink and source organs. The production of stomata, which consist of a pore between two adjacent guard cells, are central to plant adaptation to changing environment conditions. In this context, ABA is a core modulator of environmentally determined stomatal development. It is well established that ABA reduces stomatal aperture but in addition, this hormone also enhances stomatal production. For example, when grown at very high CO2 levels, Arabidopsis lines with defects in ABA biosynthesis have reduced stomatal production. By contrast, under standard conditions, these ABA biosynthetic mutants show increased stomatal production. However, the molecular mechanism(s) underpinning this regulation remain largely unknown. In this review, we summarise the current knowledge concerning sucrose transport and ABA signalling relating to stomatal production. Further, we provide fresh insights into the possible function of photosynthetic product induced‐ABA as a balancer of carbohydrate accumulation between sink and source organs, to control stomatal production and thereby to adjust stress responses and acclimation in plants, by controlling sucrose transport systems.
Visual activity enhances neuronal excitability in thalamic relay neurons
Authors: Duménieu Maël , Fronzaroli-Molinieres Laure , Naudin Loïs , Iborra-Bonnaure Cécile , Wakade Anushka , Zanin Emilie , Aziz Aurore , Ankri Norbert , Incontro Salvatore , Denis Danièle , Marquèze-Pouey Béatrice , Brette Romain , Debanne Dominique , Russier Michaël
Published: January 2025

Amblyopia, a highly prevalent loss of visual acuity, is classically thought to result from cortical plasticity. The dorsal lateral geniculate nucleus (dLGN) has long been held to act as a passive relay for visual information, but recent findings suggest a largely underestimated functional plasticity in the dLGN. However, the cellular mechanisms supporting this plasticity have not yet been explored. We show here that monocular deprivation (MD), an experimental model of amblyopia, reduces the intrinsic excitability of dLGN cells. Furthermore, dLGN neurons exhibit long-term potentiation of their intrinsic excitability (LTP-IE) when suprathreshold afferent retinal inputs are stimulated at 40 hertz or when spikes are induced with current injection. LTP-IE is observed after eye opening, requires calcium influx, is expressed through the down-regulation of Kv1 channels, and is altered following MD. In conclusion, our study provides the first evidence for intrinsic plasticity in dLGN neurons induced by natural stimuli.
De novo design of peptide binders to conformationally diverse targets with contrastive language modeling
Authors: Bhat Suhaas , Palepu Kalyan , Hong Lauren , Mao Joey , Ye Tianzheng , Iyer Rema , Zhao Lin , Chen Tianlai , Vincoff Sophia , Watson Rio , Wang Tian Z. , Srijay Divya , Kavirayuni Venkata Srikar , Kholina Kseniia , Goel Shrey , Vure Pranay , Deshpande Aniruddha J. , Soderling Scott H. , DeLisa Matthew P. , Chatterjee Pranam
Published: January 2025

Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)–based contrastive learning architecture. By integrating these generative and discriminative steps, we create a Peptide Prioritization via CLIP (PepPrCLIP) pipeline and validate highly ranked, target-specific peptides experimentally, both as inhibitory peptides and as fusions to E3 ubiquitin ligase domains. PepPrCLIP-derived constructs demonstrate functionally potent binding and degradation of conformationally diverse, disease-driving targets in vitro. In total, PepPrCLIP empowers the modulation of previously inaccessible proteins without reliance on stable and ordered tertiary structures.
Digital channel–enabled distributed force decoding via small datasets for hand-centric interactions
Authors: Tang Yifeng , Li Gen , Zhang Tieshan , Ren Hao , Yang Xiong , Yang Liu , Guo Dong , Shen Yajing
Published: January 2025

Tactile interfaces are essential for enhancing human-machine interactions, yet achieving large-scale, precise distributed force sensing remains challenging due to signal coupling and inefficient data processing. Inspired by the spiral structure of
Aloe polyphylla
and the processing principles of neuronal systems, this study presents a digital channel–enabled distributed force decoding strategy, resulting in a phygital tactile sensing system named PhyTac. This innovative system effectively prevents marker overlap and accurately identifies multipoint stimuli up to 368 regions from coupled signals. By integrating physics into model training, we reduce the dataset size to just 45 kilobytes, surpassing conventional methods that typically exceed 1 gigabyte. Results demonstrate PhyTac’s impressive fidelity of 97.7% across a sensing range of 0.5 to 25 newtons, enabling diverse applications in medical evaluation, sports training, virtual reality, and robotics. This research not only enhances our understanding of hand-centric actions but also highlights the convergence of physical and digital realms, paving the way for advancements in AI-based sensor technologies.
Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages
Authors: Stoolman Joshua S. , Grant Rogan A. , Billingham Leah K. , Poor Taylor A. , Weinberg Samuel E. , Harding Madeline C. , Lu Ziyan , Miska Jason , Szibor Marten , Budinger GR Scott , Chandel Navdeep S.
Published: January 2025

Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mitochondria ETC complex III (CIII)–deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow–derived macrophages (BMDMs) isolated from these mitochondria CIII–deficient mice released less IL-10 than controls following TLR3 or TLR4 stimulation. Unexpectedly, restoring mitochondrial respiration without generating superoxide using alternative oxidase (AOX) was not sufficient to reverse LPS-induced endotoxic shock susceptibility or restore IL-10 release. However, activation of protein kinase A (PKA) rescued IL-10 release in mitochondria CIII-deficient BMDMs following LPS stimulation. In addition, mitochondria CIII deficiency did not affect BMDM responses to interleukin-4 (IL-4) stimulation. Thus, our results highlight the essential role of mitochondria CIII–generated superoxide in the release of anti-inflammatory IL-10 in response to TLR stimulation.
Humanoid robot learning of complex behaviors with LLMs
Authors: Matsiko Amos
Published: January 2025

Learning complex behaviors by humanoid robots could be achieved with natural interactions aided by large language models.
Triple knockdown of
CD11a
,
CD49d
, and
PSGL1
in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice
Authors: Wang Hongye , Wu Zhaorong , Cui Dan , Bian Linke , Zheng Zhigang , Zhu Jiufei , Geng Haigang , Sun Zhen , Pan Yixiao , Shi Yaoping , Yi Qiaoyong , Song Zhenyu , Li Yantao , Shen Kangjie , Li Yuan , Shen Weiming , Yan Hexin , Hao Ruidong , Sun Minmin , Zhang Shuangshung , Zhang Chuanjie , Jin Haojie , Zhai Bo
Published: January 2025

Chimeric antigen receptor (CAR)–T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue. Here, we demonstrated that targeting the cell adhesion and migration molecules lymphocyte function–associated antigen 1 (LFA-1; CD11a/CD18) and very late activation antigen 4 (VLA-4; CD49d/CD29) with blocking antibodies reduced the on-target, off-tumor toxicity of CAR-T cells in mice. To translate this observation into improved CAR-T cell therapy, we either knocked out both
CD11a
and
CD49d
or knocked down
CD11a
and
CD49d
along with
PSGL1
, another cell adhesion molecule, in CAR-T cells. We found that these modified CAR-T cells exhibited reduced on-target, off-tumor toxicity in vivo without affecting CAR-T cell efficacy. Furthermore, we showed that this approach promoted T cell memory formation and decreased tonic signaling. On the basis of these data, we engineered a human version of these low-toxicity CAR-T cells and further validated the feasibility of this approach in vitro and in vivo. Together, these results provide a potential solution to address the clinical challenge of on-target, off-tumor toxicity in CAR-T therapy.
Ancient schwannoma of the submandibular gland
Authors: Sittisak Nuttawut , Kiatmontri Jinatta , Uaangkanon Sumet , Sirimahachaiyakul Pornthep
Published: January 2025

Schwannomas, benign tumours derived from Schwann cells, exhibit slow growth rates and are commonly found extracranially in the head, neck and extremities. However, intraoral and salivary gland schwannomas are less frequent. Ancient schwannomas, characterised by histological degenerative changes, represent a rare variant.

This report pertains to a case study involving a man in his 40s who presented with a slow, progressive and painless mass in the right submandibular region persisting over 3 years.

CT revealed a well-defined multiloculated cystic mass in the right submandibular gland, later confirmed as an ancient schwannoma on excision and histological examination. Immediate postoperative complications included right marginal mandibular nerve palsy, fully resolving within 12 months. No recurrent tumours were detected in subsequent physical examinations and imaging.

Ancient schwannomas, although rare, can occur in the submandibular gland. Thorough multimodal diagnostic approaches are essential for accurate differentiation from other submandibular masses.
Pioneering robotic-assisted Davydov vaginoplasty for Mayer-Rokitansky-Küster-Hauser syndrome
Authors: Panwar Vikas Kumar , Heda Ayush , Singh Gupchee , Bahadur Anupama
Published: January 2025

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder marked by the congenital absence of the uterus and vagina. Patients with this condition often present with primary amenorrhoea and normal secondary sexual characteristics. The diagnosis of MRKH syndrome has profound implications for a patient’s fertility and psychological well-being, necessitating a multidisciplinary approach that includes psychosocial support. We present a case of a young woman with MRKH syndrome who underwent robot-assisted Davydov’s vaginoplasty for neovaginal creation. The procedure used the enhanced precision and visualisation of robotic technology, resulting in the successful formation of a 7 cm neovagina with minimal postoperative complications. The robotic approach to Davydov vaginoplasty, though relatively unexplored in MRKH syndrome, presents several advantages over conventional methods, including greater surgical precision, reduced operative time and quicker recovery. This case highlights the potential benefits of robotic-assisted surgery in MRKH syndrome, offering improved outcomes and contributing to the limited literature on this advanced surgical approach.
Veno-venous ECMO intervention for respiratory failure after trauma from a motor vehicle collision
Authors: Lian Tony , Lumsden Emma , Pincus Jason , Chan Justin , Rudd Michael
Published: January 2025

Extracorporeal membrane oxygenation (ECMO) has emerged as a salvage therapy in refractory respiratory failure. Within the literature, there is evidence to support the use of ECMO in severe thoracic trauma; however, there is minimal information on its applicability in mild to moderate thoracic trauma. This report describes a man in his 50s who suffered thoracic trauma following a motor vehicle accident, who, despite maximal medical therapy, experienced deterioration in respiratory function, requiring the commencement of veno-venous ECMO on day 5 post injury and subsequently achieved excellent functional recovery.
Chronic enteropathy associated with SLCO2A1 from North India: a rare monogenic condition mimicking Crohn’s disease
Authors: Prasad Gaurav , Kulkarni Kaushal , Dhua Anjan Kumar , Malik Rohan
Published: January 2025

Multiple chronic ulcers of the small intestine are primarily attributed to Crohn’s disease. Other differential diagnoses include rare monogenic disorders caused by mutations inPLA2G4AandSLCO2A1, the latter responsible for chronic enteropathy associated withSLCO2A1(CEAS), a condition mainly reported in Asian patients. We present the case of a 10-year-old girl from India with a 5-year history of abdominal pain, altered bowel habits and failure to gain weight. Despite multiple admissions and treatment with steroids, immunomodulators and biologics, her symptoms persisted. Exome sequencing confirmed CEAS, and radiographic imaging revealed multiple strictures in the small intestine, confirmed during laparotomy. Multiple Heineke-Mikulicz type strictureplasties were performed. This case underscores the importance of considering CEAS in patients with recurrent small intestinal ulcerations, particularly in the presence of concentric strictures, and highlights the role of genetic testing forSLCO2A1mutations.
Neurodevelopmental outcomes after infant heart surgery for congenital heart disease: a hospital-based multicentre prospective cohort study from India
Authors: Raj Manu , Chattopadhyay Amitabha , Gupta Saurabh Kumar , Jain Shreepal , Sastry Usha M K , Sudevan Remya , Sharma Meenakshi , Pragya Pragati , Shivashankar Roopa , Sudhakar Abish , Radhakrishnan Anjana , Parveen Sana , Patil Sakshi , Naik Shamika , Das Shilpa , Kumar Raman Krishna
Published: January 2025

Background

Neurodevelopmental disability is a common long-term concern following surgery for congenital heart disease (CHD). Little information is available from low-resource environments where the majority of children with CHD are born. Several challenges in the CHD care continuum exist in such environments.

Methods

We followed 1346 infants who were operated for CHD using cardiopulmonary bypass from five paediatric cardiac programmes across India. The neurodevelopmental assessment was done using the Developmental Assessment Scale for Indian Infants (DASII) at 6 months after surgery.

Results

A total of 1145 (94.8%) infants were alive at 6 months and 127 (11.1%) were lost to follow-up. The mean age of participants at baseline was 5.2 (3.6) months. The mean motor developmental quotient (DMoQ) and mental developmental quotient (DMeQ) of the remaining 1018 infants were 81.8 (69.5, 93.0) and 87.7 (77.1, 95.7), respectively. A total of 262 (25.7%) infants had motor developmental delay and 157 (15.4%) had mental developmental delay. Syndromic association, younger age at surgery, duration of mechanical ventilation and head circumference were significantly associated with DMoQ. The DMeQ was associated with syndromes, duration of hospital and intensive care unit stay and socioeconomic status. The preoperative condition did not impact mental and motor development. Motor clusters with maximum delay included body control and locomotion. Mental clusters with maximum delay included reaching and manipulation, social interaction-imitative behaviour and vocabulary comprehension.

Conclusions

Survivors of infant heart surgery experience significant motor and mental neurodevelopmental delay. This delay is associated with similar factors reported by earlier studies. As more high-risk infants undergo cardiac surgery in low-resource settings, a growing population will require significant societal resources for neurodevelopmental assessment as well as neurodevelopmental rehabilitation. These resources include trained personnel for comprehensive developmental assessment of survivors of CHD surgery, as well as infrastructural requirements for dedicated assessment rooms in centres providing surgical care for CHD patients.
Interplay of chiral transitions in the standard model
Authors: Gies Holger , Schmieden Richard , Zambelli Luca
Published: January 2025

We investigate nonperturbative aspects of the interplay of chiral transitions in the standard model in the course of the renormalization flow. We focus on the chiral symmetry breaking mechanisms provided by the QCD and the electroweak sectors, the latter of which we model by a Higgs-top-bottom Yukawa theory. The interplay becomes quantitatively accessible by accounting for the fluctuation-induced mixing of the electroweak Higgs field with the mesonic composite fields of QCD. In fact, our approach uses dynamical bosonization and treats these scalar fields on the same footing. Varying the QCD scale relative to the Fermi scale we quantify the mutual impact of the symmetry-breaking mechanisms, specifically the departure from the second order quantum phase transition of the pure Yukawa sector in favor of a crossover upon the inclusion of the gauge interactions. This allows to discuss the “naturalness” of the standard model in terms of a pseudo-critical exponent which we determine as a function of the ratio of the QCD and the Fermi scale. We also estimate the minimum value of the W boson mass in absence of the Higgs mechanism.
$$\varLambda $$CDM model against gravity-thermodynamics conjecture: observational constraints after DESI 2024
Authors: Shahhoseini N. , Malekjani M. , Khodam-Mohammadi A.
Published: January 2025

In the context of the gravity-thermodynamics conjecture based on the Tsallis entropy-area relation, we investigate the standard

$$\varLambda $$

Λ

CDM cosmology and examine some potential deviations from it. Utilizing recent updates from geometrical datasets, including the DESI BAO measurements (2024), Planck CMB anisotropy measurements (2018), and the Pantheon+ catalogue for SNIa (2022), we conduct a thorough analysis via the window of Tsallis cosmology. In the first step, our analysis reveals no significant deviation from the standard model when using DESI BAO data alone, Pantheon+ data alone, or a combination of both. In the next step, we incorporate all datasets by adding the CMB data to our analysis, indicating a potential deviation from the standard model within the framework of Tsallis cosmology. Imposing the Planck prior to the sound horizon at the baryon drag epoch, we observe support for the standard model and consistency between our constraints on the Hubble constant and the Planck value. Finally, we compare the Tsallis and

$$\varLambda $$

Λ

CDM cosmologies using the Akaike Information Criterion (AIC).
Signal Feature Coverage and Testing for CPS Dataflow Models
Authors: Bartocci Ezio , Mariani Leonardo , Ničković Dejan , Yadav Drishti
Published: January 2025

Design of cyber-physical systems (CPS) typically involves dataflow modelling. The structure of dataflow models differs from the traditional software, making standard coverage metrics not appropriate for measuring the thoroughness of testing. To address this limitation, this paper proposes
signal feature coverage
as a new coverage metric for systematically testing CPS dataflow models. We derive signal feature coverage by leveraging signal features. We developed a testing framework in Simulink
®
, a popular dataflow modelling and simulation environment, that automates the generation and execution of test cases based on the defined coverage metric. We evaluated the effectiveness of our approach by carrying out experiments on five Simulink
®
models tested against ten Signal Temporal Logic specifications. We compared our coverage-based testing approach to adaptive random testing, falsification testing, output diversity-based approaches, and testing using MathWorks’ Simulink
®
Design Verifier™. The results demonstrate that our coverage-based testing approach outperforms the conventional techniques regarding fault detection capability.
Atomistic Insights into Elemental Two-Dimensional Materials and Their Heterostructures
Authors: Rajak Soumyajit , Schultz Jeremy F. , Li Linfei , Jiang Nan
Published: January 2025

Inspired by the success of graphene, two-dimensional (2D) materials have been at the forefront of advanced (opto-)nanoelectronics and energy-related fields owing to their exotic properties like sizable bandgaps, Dirac fermions, quantum spin Hall states, topological edge states, and ballistic charge carrier transport, which hold promise for various electronic device applications. Emerging main group elemental 2D materials, beyond graphene, are of particular interest due to their unique structural characteristics, ease of synthetic exploration, and superior property tunability. In this review, we present recent advances in atomic-scale studies of elemental 2D materials with an emphasis on synthetic strategies and structural properties. We also discuss the challenges and perspectives regarding the integration of elemental 2D materials into various heterostructures.
Mapping Sentinel Vessels in Uveal Melanomas Using Laser Speckle Contrast Imaging
Authors: Engqvist Linn , Dahlstrand Ulf , Sheikh Rafi , Malmsjö Malin
Published: January 2025

Introduction: Sentinel vessels provide an important early indication of underlying ocular neoplasm. To date, there is no non-invasive technique available for imaging and mapping of their vascular supply, which remains largely unstudied. We aimed to map sentinel vessels in uveal melanomas non-invasively by laser speckle contrast imaging (LSCI).

Case presentations: This report describes a case series of four patients undergoing enucleation due to uveal melanoma. Perfusion was imaged using LSCI during the successive detachment of the four rectus muscles, with their ciliary arteries, and the optic nerve with its ophthalmic artery. Tumor location and possible extrascleral growth were analyzed histopathologically.

Results: Sentinel vessels in uveal melanoma could be visualized non-invasively using LSCI, appearing broader and tortuous compared to surrounding vessels. The perfusion in the sentinel vessels was 24-94% higher than in the episcleral vessels. The origin of the sentinel vessel could be determined by perfusion monitoring during the successive detachment of the rectus muscles and the optic nerve. In three patients the sentinel vessel was supplied by the anterior ciliary arteries, and in one patient by the ophthalmic artery. In one of the cases, the sentinel vessel was not visible upon visual inspection.

Conclusion: This is the first study of its kind demonstrating detailed mapping of sentinel vessels in uveal melanoma using LSCI. LSCI shows potential for the detection of sentinel vessels before they are visible in slit lamp examination. Vascular changes are a hallmark of tumor growth, and non-invasive imaging with LSCI may be a useful diagnostic tool for the detection of uveal melanoma.
Fournier’s Gangrene leads to lower Quality of Life and Self-esteem
Authors: Lenart Sebastian , Dorfinger Julia , Graf Sebastian , Wimpissinger Florian , Schallmayer Dennis , Huber Livia , Bachler Valentin , Lusuardi Lukas , Krishnakumar Malavika , Madersbacher Stephan , Lotterstätter Michael
Published: January 2025

Introduction: Fournier’s gangrene (FG) is a life-threatening necrotizing infection of the perineal, genital, or perianal regions, often requiring extensive surgical intervention and prolonged recovery. Despite advances in acute management, the long-term impact of FG on patients’ self-esteem and quality of life remains underexplored.
Methods: This retrospective study included 48 patients treated for FG at seven urological centres in Austria between 2017 to 2022. Several in-house data were collected and patients were contacted after a mean of 4.5yrs to complete a questionnaire including the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), Short-Form (SF12) quality of life questionnaire, and the Rosenberg self-esteem scale (RSE).
Results: The study recruited 48 patients with a median age of 64 years; 58.7% required intensive care unit (ICU) stays due to infection (median duration. 6 days). The in-house mortality rate was 8.3%. Survivors (n=44) had a median hospitalization of 16 days. They were contacted by mail, 18 completed the questionnaire. There was a high prevalence of urinary symptoms and erectile dysfunction, wound pain, and impaired quality of life. Severe erectile dysfunction (IIEF-5 score ≤7) was reported by 46.2%, and 38.9% reported Visual Analog Scale (VAS) pain score ≥4. Impaired self-esteem (mean RSE score: 12.4) correlated with functional impairments, including urinary symptoms (IPSS ≥20 in 55.6%), erectile dysfunction, and wound-related pain. Physical and mental health were strongly associated with decreased self-esteem, with hypertension (61.1%) and alcohol abuse (16.7%) negatively impacting outcomes.
Conclusions: FG negatively impacts patients’ self-esteem and quality of life, particularly in the presence of pre-existing risk factors. The findings highlight the importance of integrated rehabilitation approaches to mitigate long-term psychological and functional impairments.
Hypotensive Episodes Identified on 24-Hour Ambulatory Blood Pressure and Impaired Cognitive Function: Insights From the SPRINT Study
Authors: Zhang Wenxin , Redline Susan , Viswanathan Anand , Ascher Simon B. , Hari Darshana , Juraschek Stephen P. , Tzourio Christophe , Drawz Paul E. , Lipsitz Lewis A. , Mittleman Murray A. , Ma Yuan
Published: January 2025

BACKGROUND:

Hypotensive episodes detected by 24-hour ambulatory blood pressure (BP) monitoring capture daily cumulative hypotensive stress and could be clinically relevant to cognitive impairment, but this relationship remains unclear.

METHODS:

We included participants from the Systolic Blood Pressure Intervention Trial (receiving intensive or standard BP treatment) who had 24-hour ambulatory BP monitoring measured near the 27-month visit and subsequent biannual cognitive assessments. We evaluated the associations of hypotensive episodes (defined as systolic BP drops of ≥20 mm Hg between 2 consecutive measurements that reached <100 mm Hg) and hypotensive duration (cumulative time of systolic BP <100 mm Hg) with subsequent cognitive function using adjusted linear mixed models. We further assessed 24-hour average BP and variability.

RESULTS:

Among 842 participants with treated hypertension (mean age, 71±9 years; 29% women), the presence (versus absence) of recurrent hypotensive episodes (11%) was associated with lower digit symbol coding scores (difference in
Z
scores, −0.249 [95% CI, −0.380 to −0.119]) and faster declines (difference in
Z
score changes, −0.128 [95% CI, −0.231 to −0.026]). A consistent dose-response association was also observed for longer hypotensive duration with worse Montreal Cognitive Assessment and digit symbol coding scores. The association with digit symbol coding scores remained significant after further adjusting for 24-hour average BP and variability and was not observed for hypotension defined by clinic, orthostatic, or 24-hour average BP. Intensive BP treatment increased 24-hour hypotensive episodes and modified its association with the decline in digit symbol coding score.

CONCLUSION:

Twenty-four–hour hypotensive episodes were associated with worse cognitive function, especially in processing speed, and could be a novel marker for optimal BP control and dementia prevention.