bluuebunny/crossref_metadata_2025 huggingface dataset:
High levels of heat stress among sugarcane workers in Thailand
Authors: Tantipanjaporn Tadpong , Povey Andrew , Shiels Holly A , van Tongeren Martie
Published: January 2025

Objectives

With continued global warming, the effects of elevated temperatures on the health of agricultural workers are a particular concern. This study characterized the levels of heat stress in Thai sugarcane workers and investigated whether season and harvesting method were associated with it.

Methods

Three hundred sugarcane workers in Nakhon Sawan Province, Thailand, were recruited, and information on demographics, working conditions, and clothing characteristics was collected from participants during the cooler months (n = 152 participants, mid-January to mid-February) and hotter month (n = 148, March). Heat stress was measured using the Wet Bulb Globe Temperature (WBGT) index, and the WBGT instruments were operated for a full work shift in the sugarcane fields where the participants worked. One-hour time weighted average (TWA) effective WBGT (WBGTeff-1hrTWA) estimates were determined for different times of the day based on the measured WBGT and clothing adjustment factor.

Results

The average WBGTeff-1hrTWA in the cooler months ranged from 22.5 °C during the early morning to 31.3 °C during the hottest time of the day, and for the hotter month, it ranged from 25.4 °C to 33.9 °C, respectively. The measured WBGT, natural wet-bulb temperature (Tnwb), dry-bulb temperature (Tdb), globe temperature (Tg), air velocity (Av), and absolute water vapor pressure (ea) were all statistically significantly higher in the hotter month than in the cooler months. Harvesting during the hotter month and harvesting burnt sugarcane were significantly associated with increased effective WBGT. The harvesters’ heat stress in both seasons exceeded the American Conference of Governmental Industrial Hygienists - Threshold limit value for 72.7% of the working time in the cooler months and 90.9% in the hotter month.

Conclusions

The heat stress in Thai sugarcane workers was high in both seasons, particularly in the hotter month and when harvesting burnt sugarcane. This results in a very high risk of developing heat-related health effects, and measures are needed to reduce heat stress. Heat stress in agricultural and other outdoor work in tropical climates is an immediate and growing problem.
Unveiling cross-reactivity: implications for immune response modulation in cancer
Authors: Pretti Marco Antônio M , Vieira Gustavo Fioravanti , Boroni Mariana , Bonamino Martín H
Published: January 2025

Antigen recognition by CD8+ T-cell receptors (TCR) is crucial for immune responses to pathogens and tumors. TCRs are cross-reactive, a single TCR can recognize multiple peptide-Human Leukocyte Antigen (HLA) complexes. The study of cross-reactivity can support the development of therapies focusing on immune modulation, such as the expansion of pre-existing T-cell clones to fight pathogens and tumors. The peptide-HLA (pHLA) surface has previously been used to identify TCR cross-reactivities. In the present work, we sought to perform a comprehensive analysis of peptide-HLA by selecting thousands of human and viral epitopes. We profit from established docking models to identify features from different spatial perspectives of HLA-A*02:01, explore similarities between self and non-self epitopes, and list potential cross-reactive epitopes of therapeutic interest. A total of 2631 unique epitopes from representative viral proteins or human proteins were modeled. We were able to demonstrate that cross-reactive CDR3 sequences from public databases recognize epitopes with similar electrostatic potential, charge, and spatial location. Using data from published studies that measured T-cell reactivity to mutated epitopes, we observed a negative correlation between epitope dissimilarity and T-cell activation. Most analysed cancer epitopes were more similar to self epitopes, yet we identified features distinguishing those more similar to viral antigens. Finally, we enumerated potential cross-reactivities between tumoral and viral epitopes and highlighted some challenges in their identification for therapeutic use. Moreover, the thousands of peptide-HLA complexes generated in our work constitute a valuable resource to study T-cell cross-reactivity.
Multidimensional structural analyses revealed a correlation between thalamic atrophy and white matter degeneration in idiopathic dystonia
Authors: Xu Jinping , Cheng Qinxiu , Zhang Yue , Luo Yuhan , Zhong Linchang , Liu Huiming , Zhang Haoran , Yang Zhengkun , Zhang Jiana , Ou Zilin , Yan Zhicong , Peng Kangqiang , Liu Gang
Published: January 2025

Although aberrant changes in grey and white matter are core features of idiopathic dystonia, few studies have explored the correlation between grey and white matter changes in this disease. This study aimed to investigate the coupling correlation between morphological and microstructural alterations in patients with idiopathic dystonia. Structural T1 imaging and diffusion tensor imaging were performed on a relatively large cohort of patients. Multidimensional structural analyses, including voxel-based analyses, voxel-based morphology, fixel-based analyses and surface-based morphometry, were performed to explore these structural alterations. Probabilistic tractography and correlation analyses were employed to examine these relationships. A total of 147 patients with idiopathic dystonia and 137 healthy controls were recruited in this study. There were no significant differences in the cortical morphometry between patients with idiopathic dystonia and healthy controls using voxel- and surface-based morphometry. However, the grey matter volume of the bilateral thalamus, fractional anisotropy in the right anterior corona radiata, right retrolenticular part of the internal capsule and right posterior corona radiata, and the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and left area 5 m, were significantly decreased in patients with idiopathic dystonia compared with those in healthy controls. Furthermore, the reduced grey matter volume in the right thalamus not only correlated with the disease duration but also with the reduced fractional anisotropy in the right posterior corona radiata and decreased the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and the left area 5 m in patients with idiopathic dystonia. These findings suggest that the thalamus is structurally impaired in idiopathic dystonia and that microstructural disruption in thalamocortical projections occurs secondary to thalamic atrophy.
Left coronary ostial isolation in a young boy caused by a dysplastic aortic valve: a case report
Authors: Fitzgerald Nicholas , Liava’a Matthew , Gnanappa Ganesh , Ayer Julian
Published: January 2025

Background

Ischaemic cardiac chest pain and coronary artery abnormalities are uncommon in children. The long-term implications of missed or delayed diagnosis are myocardial ischaemia and risk of sudden cardiac death. Improvement in non-invasive imaging has made diagnosis and surgical planning possible with multi-modal imaging.

Case summary

A 12-year-old boy with ischaemic chest pain caused by isolation of the left coronary ostium in the context of a dysplastic aortic valve. There was a delay to formal diagnosis. Surgical aortic valve repair resulted in complete resolution of symptoms. Ethics approved (SCHN: CCR2023/5).

Discussion

Isolation of the left coronary ostium caused by a dysplastic aortic valve (without supravalvar stenosis) is an example of a rare cause of ischaemic chest pain in children. To our knowledge, only 10 paediatric case reports are published in English. In reported cases, presenting features varied from poor feeding and a murmur in infants to chest pain, syncope, or cardiac arrest in adolescents. Historically, angiography during a cardiac catheter procedure was required for diagnosis; however, improvements in non-invasive imaging techniques have resulted in the diagnosis being possible on echocardiography (supported by computed tomography angiography or cardiac magnetic resonance imaging).
Small-scale genetic differentiation in mean flowering time, but not in plasticity, along a geothermal heating gradient
Authors: Valdés Alicia , Helmutsdóttir Vigdís F , Marteinsdóttir Bryndís , Ehrlén Johan
Published: January 2025

Genetic differentiation in traits is assumed to frequently occur in response to divergent natural selection. For example, developmental traits might respond to differences in climate. However, little is known about when and at which spatial scales environmental differences lead to genetic differentiation, and to what extent there is genetic differentiation also in trait plasticity. Using a crossing design and a greenhouse heating experiment, we investigated genetic differentiation in thermal sensitivity of flowering time in a perennial herb along small-scale gradients in geothermal soil heating in Iceland. We found additive genetic variation in both flowering time and thermal plasticity of flowering time. Genetic differentiation in the median flowering date of individuals showed a counter-gradient pattern; flowering being earlier at higher greenhouse temperatures, while at a given temperature individuals originating from warmer soils flowered later than individuals from colder soils. We found no corresponding pattern for plasticity, suggesting that genetic differentiation in phenology in response to soil heating has occurred through changes in trait means rather than in plasticity. Findings such as these identifying genetic trait differentiation along an environmental gradient are key to understand how environmental variation can drive the process of local adaptation, and to predict responses to future environmental changes.
Hyperbolicity and Model-Complete Fields
Authors: Szachniewicz Michał , Ye Jinhe
Published: January 2025

We study model-complete fields that avoid a given quasi-project variety $V$. There is a close connection between hyperbolicity of $V$ and the existence of the model companion for the theory of characteristic-zero fields avoiding rational points on $V$. This gives a model theoretic notion of hyperbolicity that we call excludability. In particular, we show that if $V$ is a Brody hyperbolic projective variety over ${\mathbb{Q}}$ with $V({\mathbb{Q}}) = \varnothing $, then the model companion, called $V\textrm{XF}$, exists. We also study some model-theoretic properties of $V\textrm{XF}$. This extends the results for curves by Will Johnson and the second author.
External quality assurance (EQA) network in South and South-East Asia: experience and results from an international EQA programme in One Health sector reference laboratories
Authors: Kostyanev Tomislav , Al-Mir Hiba , Prifti Kristi , Rasmussen Lone Brink , Abegaz Freshwork Ayalew , Teixeira Dos Santos Patrícia , Kwon Soo-Young , Prathan Rangsiya , Luang Tongkum Taradon , Chanchaithong Pattrarat , Santanirand Pitak , Kamjumphol Watcharaporn , Mogeni Ondari D , Guarnacci Tobin , Poudyal Nimesh , Holm Marianne , Paveenkittiporn Wantana , Chuanchuen Rungtip , Hendriksen Rene S
Published: January 2025

Objectives

External quality assurance (EQA) is an objective tool to assess laboratories’ diagnostic performance and their adherence to recognized international standards. External Quality Assessment in Asia (EQASIA) is an EQA network in South and South-East Asia established in 2020 with the aim of improving the quality of bacteriology diagnostics across all One Health sectors in the region. The aim of this paper is to provide a comprehensive overview of the EQA results collected from the EQASIA network and to assess improvements among the participating laboratories.

Methods

Six EQA rounds were conducted between 2021 and 2023, each composed of different panels of WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) and The Food and Agriculture Organization of the United Nations (FAO) priority pathogens of interest to both the human and animal health sector.

Results

Between 24 and 32 laboratories signed up for six EQA rounds (EQA1–6). Participating laboratories were able to isolate and correctly identify most of the isolates across the EQA panels except for the Campylobacter spp. and Enterococcus spp. panels. The overall performance of laboratories across the six EQAs was between 75% and 100% (average 93.3% and median 93.6%). The obtained results showed a significant improvement in laboratories’ performance over time.

Conclusions

Laboratory capacity development and quality assurance in a microbiology laboratory are of particular importance especially in the context of antimicrobial resistance (AMR) and One Health surveillance. The EQASIA programme has the potential to validate laboratories’ performance in detecting important One Health pathogens, generating reliable data for effective surveillance to curb AMR.
Impact of climate change on the distribution of the citrus longhorned beetle Anoplophora chinensis (Coleoptera: Cerambycidae) and its host plants, Castanea mollissima and Castanea seguinii: a predictive analysis using optimized MaxEnt models
Authors: Zhang Liang , Wang Ping , Xie Guanglin , Wang Wenkai
Published: January 2025

The Anoplophora chinensis (Coleoptera: Cerambycidae) (Forster), a serious phytophagous pest threatening Castanea mollissima Blume and Castanea seguinii Dode, poses risks of ecological imbalance, significant economic loss, and increased management difficulties if not properly controlled. This study employs optimized MaxEnt models to analyze the potential distribution areas of A. chinensis and its host plants under current and future climate conditions, identifying their movement pathways and relative dynamics. Results indicate that all models achieved an average AUC value exceeding 0.86, demonstrating low complexity and high predictive accuracy. The key climatic variables influencing the geographic distribution of A. chinensis and its host plants include temperature and moisture-related bioclimatic variables such as mean diurnal range, minimum temp of coldest month, mean temp of wettest quarter, annual precipitation, precipitation of driest month, and precipitation seasonality. Under both current and future conditions, these 3 species are primarily distributed in the southwestern regions of China. Notably, the suitable growth area for all 3 species shows varying degrees of increase. Additionally, C. mollissima and C. seguinii exhibit a trend of eastward displacement in response to climate change. Overall, the findings provide significant practical value for the monitoring, early warning, and targeted control strategies for A. chinensis. Furthermore, these results offer a basis for timely conservation strategies to mitigate the potential impacts of climate change.
Chlorhexidine gluconate application, diabetes, revision surgery, and extended operative time increase risk for penile implant infection
Authors: Helo Sevann , Bonakdar Hashemi Milad , Ziegelmann Matthew J , Lybbert Daniel T , Piraino Javier , Guillen Lozoya Andres H , Köhler Tobias S
Published: January 2025

Background

Chlorhexidine gluconate (CHG) (0.05%) has recently been suggested as a dip and irrigation solution at time of inflatable penile prosthesis (IPP) surgery.

Aim

This study evaluated infection rates before and after implementing CHG protocol while investigating concurrent risk factors contributing to post operative infections.

Methods

A retrospective, consecutive cohort study was performed that included patients who underwent insertion of a Coloplast Titan IPP including both virgin and revision cases between 2021 and 2024. Cases performed from January 2021 to August 2022 utilized rifampin/gentamicin for dip and vancomycin/gentamicin for irrigation (ABX), whereas those from October 2022 to May 2024 utilized CHG for both dip and irrigation. Perioperative risk factors including dip and irrigation solution used at time of surgery were compared between groups.

Outcomes

We defined the incidence of postoperative infection and risk factors associated with infection in each group.

Results

The incidence of infection was significantly higher in the 0.05% CHG group (13/377) compared to the ABX group (0/320) (P < .001). When analyzed separately by subgroup, virgin cases treated with CHG for dip and irrigation demonstrated a significantly higher infection rate (7/315) compared to those in the ABX group (0/280) (P = .012). Similarly, in revision cases, the CHG group also exhibited a significantly higher infection rate (0/40) than the ABX group (6/62) (P = .043).

Univariable analysis of the CHG cohort identified three significant risk factors for infection: diabetes mellitus (DM), extended operative time (OP), and revision surgery (P = .003, .001, and < .001, respectively). Multivariable regression analysis revealed that patients with DM had a 5.7-fold increased risk of infection (OR: 5.70, P = .004), while those undergoing revision surgery faced a 5.3-fold higher risk (OR: 5.26, P = .004). Additionally, each minute increase in OP was associated with a 1% higher infection risk (OR: 1.01 per minute, P = .007). These associations remained significant after adjusting for all variables in the model.

Clinical Implications

Prosthetic surgeons should be cautious about adopting 0.05% CHG for both dip and irrigation in the absence of strong clinical evidence demonstrating its non-inferiority to antibiotic solutions.

Strengths and Limitations

This is the first clinical study reporting infection rates after IPP surgery using 0.05% CHG for both dip and irrigation. While retrospective and non-randomized, we present a relatively large sample size of patients.

Conclusions

Our findings identify four risk factors for penile prosthesis infection: usage of the 0.05% CHG solution for dip and irrigation solution of Coloplast hydrophilic-coated devices, DM, revision surgery, and extended OP.
Combining REBOUND and MESA: dynamical evolution of planets orbiting interacting binaries
Authors: Xing Zepei , Torres Santiago , Götberg Ylva , Trani Alessandro A , Korol Valeriya , Cuadra Jorge
Published: January 2025

Although planets have been found orbiting binary systems, whether they can survive binary interactions is debated. While the tightest-orbit binaries should host the most dynamically stable and long-lived circumbinary planetary systems, they are also the systems that are expected to experience mass transfer, common envelope evolution, or stellar mergers. In this study, we explore the effect of stable non-conservative mass transfer on the dynamical evolution of circumbinary planets. We present a new script that seamlessly integrates binary evolution data from the 1D binary stellar evolution code mesa into the N-body simulation code rebound. This integration framework enables a comprehensive examination of the dynamical evolution of circumbinary planets orbiting mass-transferring binaries, while simultaneously accounting for the detailed stellar structure evolution. In addition, we introduce a recalibration method to mitigate numerical errors from updates of binary properties during the system’s dynamical evolution. We construct a reference binary model in which a $2.21\, \mathrm{ M}_\odot$ star loses its hydrogen-rich envelope through non-conservative mass transfer to the $1.76\, \mathrm{ M}_\odot$ companion star, creating a $0.38\, \mathrm{ M}_\odot$ subdwarf. We find the tightest stable semimajor axis for circumbinary planets to be $\simeq 2.5$ times the binary separation after mass transfer. Accounting for tides by using the interior stellar structure, we find that tidal effects become apparent after the rapid mass transfer phase and start to fade away during the latter stage of the slow mass transfer phase. Our research provides a new framework for exploring circumbinary planet dynamics in interacting binary systems.
Diffuse alveolar haemorrhage as the initial presentation of systemic lupus erythematosus possibly triggered by Rhogam injection in a 24-year-old pregnant woman: A case report
Authors: Khanmirzaei Amir , Bozorgi Maryam , Azarinoush Gelareh , Aghaei Fatemeh , Bigdeli Asiye , Jazi Kimia , Asghari Akram , Masoumi Maryam
Published: January 2025

Diffuse alveolar haemorrhage (DAH) is an uncommon and potentially life-threatening occurrence in systemic lupus erythematosus, involving bleeding into the alveolar space caused by the disruption of the alveolar capillary basement membrane. We present a 24-year-old Persian woman with a complaint of progressively worsening shortness of breath following the administration of intramuscular Rhogam after 3 days. According to her worsening clinical condition, the pregnancy was terminated. She was admitted to the intensive care unit and intubated. Simultaneously, she developed fungal and bacterial pneumonia tolerant to therapies. After several investigations, the patient was finally diagnosed with systemic lupus erythematosus along with DAH, as the first presentation of the disease. This is the first case of a pregnant woman experiencing DAH as a lupus flare following Rhogam injection. Clinicians should be aware of the mimicry nature of lupus and the importance of immune reactions in these patients.
Tax-price elasticities of charitable giving and selection of reporting: panel study of South Korea
Authors: Kato Hiroki , Goto Tsuyoshi , Kim Youngrok
Published: January 2025

In this study, we estimate the tax-price elasticity of charitable giving and address the bias caused by the existence of unreported donations and self-selection regarding reporting on giving. To eliminate this bias, we propose a simple estimation method based on intention-to-treat analysis. Using our proposed method and the exogenous variation in tax incentives in the 2014 South Korean tax reform, we estimate the price elasticity to be −3.5 for the amount of total giving, which is more elastic than that in the standard results that do not account for unreported donations and self-selection. This result implies that the 2014 tax reform reduced the total amount of giving and that tax incentives should be expanded.
Subgenome-informed statistical modeling of transcriptomes in 25 common wheat accessions reveals cis- and trans-regulation architectures
Authors: Nomura Yasuyuki , Okada Moeko , Tameshige Toshiaki , Takenaka Shotaro , Shimizu Kentaro K , Nasuda Shuhei , Nagano Atsushi J
Published: January 2025

Common wheat is an allohexaploid, where it is difficult to obtain homoeolog-distinguished transcriptome data. Lasy-Seq, a type of 3ʹ RNA-seq, is technology efficient at obtaining homoeolog-distinguished transcriptomes. Here, we applied Lasy-Seq to obtain transcriptome data from the seedlings, second leaves, and root tips of 25 common wheat lines mainly from East Asia. Roots and seedlings were similar to each other in transcriptome profiles, but they were different from the leaves. We then asked how three homoeologous genes from different subgenomes (i.e. triads) show different levels of expression. Specifically, we examined the effects of subgenomes, lines, and their interaction on the expression levels of each homoeolog triad, separately in each tissue. Of the 19 805 homoeolog triads, 51–55% showed significant effect of subgenome, suggesting cis-regulation, whereas 24–30% showed significant effect line, suggesting trans-regulation. We also found that 7.7–9.0% triads showed significant effects of the interaction. Hierarchical clustering and co-trans regulation network analysis of homoeolog triads revealed that the patterns of expression polymorphisms among the lines were shared in different genes. Our results also implied that expression variation between lines is caused by changes in a smaller number of common trans-factors. We performed gene ontology (GO)-term enrichment analysis using newly annotated and substantially improved GO annotations, which revealed that GO terms related to each tissue-type function were enriched in genes expressed in the leaves and roots. Our information provides fundamental knowledge for the future breeding of plants possessing complex gene regulatory networks such as common wheat.
Lost in “Translation-Work”: Negotiations of Lost and Saved Language Among Ex-Charismatic Christians in Norway
Authors: Gilsvik Espen
Published: January 2025

This article explores the language negotiations among a group of Norwegian Christian Charismatic disaffiliates from a Facebook community called “The Journey” (no. “Reisen”). The analysis is based on 24 in-depth interviews and examines specific language practices of the disaffiliates, which I call translation-work. Translation-work involves substituting the religious meaning of Christian Charismatic concepts with secular meaning, allowing the term to remain in the disaffiliates’ vocabulary. Such language negotiations also reframe Charismatic experiences with secular words and actively omit relevant disaffiliation terms and concepts used in American discourse on disaffiliation. The Norwegian informants are particularly skeptical of victim-oriented terms even though they adequately fit such descriptions. The article discusses these omissions and how and why the informants engage in translation-work. It further suggests that established scholarly and popular disaffiliation terms do not precisely capture the nuances of non/religious language in this material. The article contributes to the field by providing thick descriptions of the informants’ negotiations and suggesting translation-work as a conceptualization, which gives us new sociological understandings of liminal non/religious language and experiences.
Evaluation of suitability of two tools for the diagnosis of canine visceral leishmaniasis
Authors: Garcia Valeria S , Gutiérrez Maira S , Gonzalez Verónica D G , Gugliotta Luis M , Burna Alexis , Eiras Diego , Cabeza Matías S , Arias Diego G , Guerrero Sergio A
Published: January 2025

Background

Leishmaniasis still imposes a heavy burden on many health systems and remains a public health problem. Early diagnosis in dogs, which act as a major reservoir for the pathogen, is central. The intention of epidemiologic studies is to identify the disease early, allowing rapid intervention to reduce its effects. This study aimed to develop two types of diagnostics tools, an enzyme-linked immunosorbent assay (ELISA) and a lateral flow immunochromatography assay for recognizing canine visceral leishmaniasis (CVL).

Methods

Multiwell ELISA plates were sensitized and strips were designed with the same chimeric recombinant antigen from Leishmania spp. (LeQuiDi) and the results were compared. The sera panel contained 409 samples, including 244 positives and 165 negatives. Of the 165 negative sera, 67 were obtained from Corrientes city, an endemic area for CVL in Argentina, and 98 of this group from La Plata city, a non-endemic area in Argentina (they were seropositive for other infections, as specificity control).

Results

Serum with an elevated concentration of lipids, or bilirubin, or a variable percentage of haemolysis were tested without interference. Both the sensitivity and specificity of the LeQuiDi-based tests were high: ≥93% for ELISA and ≥87% for LFIA.

Conclusions

Our study introduces LeQuiDi as a promising antigen for CVL diagnosis, regardless of the test format.
MYBL2 promotes proliferation of clear cell renal cell carcinoma by regulating TOP2A and activating AKT/mTOR signaling pathway
Authors: Huang Yawei , Xi Xiaoqing , Ye Zhenfeng , Zhang Chiyu , Jiang Yi , Yu Fanfan , Huang Gaomin
Published: January 2025

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system, and clear cell renal cell carcinoma (ccRCC) is the most common subtype. MYBL2 has been reported to be overexpressed in various tumors and associated with poor prognosis in patients, but its biological role in ccRCC remains unclear. In this study, we investigated the mRNA and protein expression levels of MYBL2 in ccRCC samples and evaluated the prognostic value of MYBL2 using TCGA dataset. In vitro functional assays were performed using CCK‐8, EdU, colony formation, cell scratch, and transwell assays, as well as in vivo tumorigenesis assays to investigate the biological functions of MYBL2 in ccRCC. Additionally, gene set enrichment analysis (GSEA) was used to explore the downstream pathways of MYBL2, which were further validated. Finally, we predicted the target genes of MYBL2 using bioinformatics and validated them using ChIP and dual‐luciferase reporter gene assays. MYBL2 expression was significantly higher in ccRCC than in adjacent normal tissues and was associated with poor prognosis. MYBL2 expression was positively correlated with the pathological tumor grade and clinical TNM stage of ccRCC patients. Knockdown of MYBL2 significantly inhibited the proliferation of renal cancer cells in vitro and in vivo, and knockdown of MYBL2 could inhibit cell invasion and migration, while overexpression of MYBL2 had the opposite effect. GSEA revealed that MYBL2 was associated with the mTOR signaling pathway and cell cycle pathway, which was confirmed by our study. Finally, we found that TOP2A was a target gene of MYBL2, and MYBL2 could bind to the TOP2A promoter to regulate its transcriptional activity, promoting the proliferation of clear cell renal cell carcinoma cells. MYBL2 emerges as a highly expressed factor that significantly correlates with adverse patient prognosis in ccRCC. Mechanistically, MYBL2 transcriptionally upregulates TOP2A, thereby modulating the proliferation of ccRCC cells. Furthermore, MYBL2 activates the mTOR signaling pathway, a critical node in the progression of ccRCC. Collectively, these findings position MYBL2 as a promising candidate for both a biological marker and a therapeutic target in the management of ccRCC.
Targeting the insular cortex for neuropathic pain modulation: Insights into synaptic and neuronal mechanisms
Authors: Kim Kyeongmin , Nan Guanghai , Kim Hee Young , Cha Myeounghoon , Lee Bae Hwan
Published: January 2025

Neuropathic pain, caused by nerve damage, greatly affects quality of life. Recent research proposes modulating brain activity, particularly through electrical stimulation of the insular cortex (IC), as a treatment option. This study aimed to understand how IC stimulation (ICS) affects pain modulation. In a rat neuropathy model, researchers used optogenetic and ICS techniques to evaluate changes in mechanical allodynia and synaptic changes, focusing on glutamate receptors (AMPAR, NR2A, NR2B). Optogenetic inhibition of IC neurons relieved pain without altering synaptic plasticity. However, repetitive ICS combined with optogenetic activation diminished the pain‐relieving effects of ICS and increased AMPAR and NR2B receptor levels. Additionally, activating inhibitory neurons also reduced pain, while repetitive activation of excitatory neurons lessened the effectiveness of ICS and was associated with heightened receptor expression. These findings suggest that inhibiting excitatory neurons or activating inhibitory neurons in the IC could help modulate pain in neuropathic conditions, shedding light on how ICS can influence pain management through changes in synaptic plasticity.
Analysis of the Biomechanical Effects of Vertebral Body Tethering With Apical Fusion
Authors: Frank Jil , Trobisch Per David , Pishnamaz Miguel , Hildebrand Frank , Praster Maximilian
Published: January 2025

Study Design.

Biomechanical study by using a multibody simulation approach.

Objective.

Objectification of spinal biomechanics after vertebral body tethering with and without apical fusion.

Summary of Background Data.

Vertebral body tethering, a motion-preserving surgical technique for correction of adolescent idiopathic scoliosis, is increasingly being used for thoracolumbar curves. However, tether breakage remains a common problem with breakage rates up to 60% for TL curves. Therefore, surgeons have begun to adapt their surgical technique by fusing the apex. The short-term clinical studies show a significant reduction of the tether breakage rate to 10%, but little is known about the biomechanical reasons. Therefore, this study analyzes the intervertebral compression and tether force in a tethered spine without apical fusion and in a tethered spine with apical fusion between L1/2.

Methods.

A multibody simulation approach was chosen to analyze the biomechanical effects of two surgical techniques during different physiological movements. The tether and intervertebral compression forces in the different instrumented segments are once analyzed for a T10 to L3 tethered spine and once for a T10 to L3 tethered with additional L1/2 fusion using an intervertebral cage.

Results.

VBT with apical fusion reduces the prevailing tether forces not only at the fused level by nearly 861 N but also at the adjacent spinal segments by around 100 N. However, a significant increase in intervertebral compression force of ~706 N can be observed, especially at the adjacent spinal segments.

Conclusion.

L1/2 fusion in a tethered spine reduces tether forces in adjacent segments and thus might decrease the rate of tether breakage. However, fusion results in increased intervertebral compression forces by up to 31% compared with an unfused spine. Long-term clinical studies are needed to further analyze and evaluate the biomechanical consequences.
Feasibility and Acceptability of Smartwatches for Use by Nursing Home Residents
Authors: Johnson Alisha Harvey , Lee Knoo , Reeder Blaine , Popejoy Lori , Vogelsmeier Amy
Published: January 2025

Smartwatch wearables are a promising health information technology to monitor older adults with complex chronic care needs. Pilot and feasibility studies have assessed smartwatch use with community-dwelling older adults, but less is known about their use in nursing homes. The purpose of this study was to test the feasibility and acceptability of smartwatch technology in a real-world nursing home setting to generate initial evidence about potential use. Using a qualitative descriptive approach, we conducted a pilot feasibility and acceptability study of smartwatch technology: Phase 1, pretrial semistructured interviews and focus groups with nursing home leaders, staff, and residents/families; Phase 2, a 7-day smartwatch trial deployment with residents; and Phase 3, posttrial semistructured interviews and focus groups. Themes related to feasibility findings included a part of the workflow and making the technology work. Themes related to acceptability findings included it's everywhere anyway, how will you protect me, knowing how you really are, more information = more control, and knowing how they are doing. These findings have important implications for the design of technology-supported interventions incorporating these devices within the unique context of residential nursing homes to best meet the needs of older adult residents, families, and staff caretakers.
Robot-assisted “Bridge” approach pancreatosplenectomy for “shoulder” pancreatic cancer: a new technique
Authors: Zhang Jianlu , Guo Junchao
Published: January 2025

Pancreatic body/ tail cancer has a worse prognosis because of late detection and early invasion into important vessels. Our team proposed the concept of “shoulder” pancreatic cancer (PC) and invented a new approach named Retrograde artery first approach pancreatosplenectomy (RAFAPS). However, we found that in some cases this approach may not be perfect. We encountered a patient who had previously undergone laparoscopic radical operation for hilar cholangiocarcinoma caused RAFAPS could not be performed. Hence, we used a new procedure based on RAFAPS to finish the pancreatosplenectomy and named it “Bridge”. After the operation, the patient recovered smoothly. We report the new technique, aiming to provide the experience for the surgical treatment of “shoulder” PC.
Wide pulse pressure as a novel predictor of contrast-induced acute kidney injury in diabetic patients undergoing primary percutaneous coronary intervention
Authors: Yilmaz Cemalettin , Güvendi Şengör Büşra , Zehir Regayip , Kaya Ahmet Ferhat , Özdil Mehmet Hasan , Kültürsay Barkin
Published: January 2025

Background

Primary percutaneous coronary intervention (p-PCI) is pivotal in managing ST-segment elevation myocardial infarction (STEMI); however, it introduces potential risks, such as contrast-induced acute kidney injury (CI-AKI). This study aimed to investigate the relationship between pulse pressure (PP) and CI-AKI incidence in diabetic patients.

Methods

In this retrospective study conducted between 2021 and 2022, 590 diabetic STEMI patients undergoing p-PCI were categorized based on the presence of wide PP. Individuals with PP ≥ 65 mmHg were classified as the ‘wide PP (+) group’, while those with PP < 65 mmHg were classified as the ‘wide PP (−) group’. To determine independent predictors of CI-AKI, multivariable logistic regression models were applied. After establishing the base model, blood pressure indices, including PP, SBP, DBP, mean arterial pressure, and pulsatility were added to the model using the stepwise selection method.

Results

Among the patients, 18.3% (n = 108) were in the wide PP (+) group, while 81.7% (n = 482) were in the wide PP (−) group. The incidence of hypertension, SBP, PP, and the risk of CI-AKI were higher in the wide PP (+) group. Multivariable analysis recognized PP, wide PP, and pulsatility as independent CI-AKI predictors [odds ratio (OR): 1.024, 95% confidence interval (CI): 1.003–1.045, P = 0.025; OR: 1.684, 95% CI: 1.025–2.769, P = 0.040; OR: 13.816, 95% CI: 2.069–92.245, P = 0.007, respectively].

Conclusion

Increased PP emerges as an independent predictor for CI-AKI in diabetic patients undergoing p-PCI.
Seizure prediction and forecasting: a scoping review
Authors: Cheng Joshua C. , Goldenholz Daniel M.
Published: January 2025

Purpose of review

This scoping review summarizes key developments in the field of seizure forecasting.

Recent findings

Developments have been made along several modalities of seizure forecasting, including long term intracranial and subcutaneous encephalogram, wearable physiologic monitoring, and seizure diaries. However, clinical translation of these tools is limited by various factors. One is the lack of validation of these tools on an external dataset. Moreover, the widespread practice of comparing models to a chance forecaster may be inadequate. Instead, the model should be able to at least surpass a moving average forecaster, which serves as a ‘napkin test’ (i.e., can be computed on the back of a napkin). The impact of seizure frequency on model performance should also be accounted for when comparing performance across studies. Surprisingly, despite the potential for poor quality forecasts, some individuals with epilepsy still want access to imprecise forecasts and some even alter their behavior based upon them.

Promising advances have been made in the development of tools for seizure forecasting, but current tools have not yet overcome clinical translation hurdles. Future studies will need to address potentially dangerous patient behaviors as well as account for external validation, the napkin test, seizure frequency dependent metrics.
Multi-Institutional Analysis of Pancreatoduodenectomy for Nonfamilial Periampullary Adenoma: A Novel Risk Score to Guide Shared Decision-Making
Authors: Mavani Parit T , Sok Caitlin , Eng Nina , Marra Angelo , Foroutani Laleh , Alseidi Adnan , Hariri Hussein , Wilson Gregory , Ahmad Syed A , Scoggins Charles , Hester Caitlin , Datta Jashodeep , Merchant Nipun , LeCompte Michael , Kim Hong Jin , Sigler Gregory , Zafar Nabeel , Weber Sharon , Prela Orjola , Carpizo Darren , Kasting Christina , Fields Ryan , Sarmiento Juan M , Russell Maria C , Shah Mihir M , Maithel Shishir K , Kooby David A
Published: January 2025

Introduction:

Pancreatoduodenectomy (PD) may occasionally be indicated for complete removal of periampullary (duodenal and ampullary) adenomas (PAs). As compared with malignant indications, PD for benign or pre-malignant disease is often associated with increased morbidity. While the Spigelman classification assesses malignancy risk for familial adenomatous polyposis (FAP)-related duodenal adenomas, no malignancy risk score (MRS) exists for non-FAP related PAs. We developed a MRS for non-FAP related PAs undergoing PD to weigh risk of malignancy and postoperative morbidity.

Methods:

We retrospectively analyzed patients with non-FAP related PA who underwent PD at eight institutions (2010-2022). Patient and lesion factors associated with final malignant pathology were identified using multivariable logistic regression to create MRS. Postoperative complications were assessed according to MRS.

Results:

Of 127 patients, 59 (46.5%) had evidence of malignancy on final pathology. The odds of malignancy were higher in patients with older age ≥65 years (OR3.2, p=0.01), bile duct ≥9mm (OR3.3, p=0.009), preoperative symptoms (OR7.7, p=0.002), and high-grade dysplasia (HGD, OR7.5, p<0.001). A MRS was derived ranging from 0 to 6: age≥65=1, bile duct≥9mm=1, symptomatic=2, HGD=2. Patients were stratified into low (MRS1–2, n=26), intermediate (MRS3–4, n=59), and high-risk groups (MRS5–6, n=26), with malignancy rates increasing with MRS (10.3%, 44.1%, and 88.2%, p<0.001). Patients in the no/low-risk group (MRS0-2) had higher odds of major postoperative complications compared with patients in the intermediate/high-risk group (MRS≥3, OR2.9, p=0.047).

Conclusion:

This novel MRS stratifies the risk of malignancy in non-FAP related PAs managed with PD. This score can be used to counsel patients who may require PD for complete tumor removal about their risk of harboring malignancy and their risk of major postoperative complications.
Cardiac tamponade revealing tuberculous pericarditis: A case report
Authors: Skalante Oumaima , Hachimi Idrissi Mariam , Cherkaoui Soukaina , Benaissa Elmostafa , Ben Lahlou Yassine , Chadli Mariama
Published: January 2025

2. Abstract

Tuberculosis remains a major public health issue in Morocco. Pulmonary tuberculosis is the most common form, but various extrapulmonary forms exist.
Tuberculous pericarditis is a rare form of extrapulmonary tuberculosis that can be complicated by cardiac tamponade, pericardial constriction, or their combination, which can threaten the patient's life. Its clinical and radiological signs are nonspecific, and the clinical presentation can be misleading and incomplete, sometimes even with an initial tamponade.
We report the case of a 68-year-old patient admitted for intense retrosternal chest pain associated with acute dyspnea, evolving in the context of weight loss and general deterioration. Additionally, she reported a history of fever and night sweats.
Clinical examination revealed a conscious, febrile, hypotensive, tachycardic, polypneic patient with good oxygen saturation, signs of right heart failure, and muffled heart sounds on auscultation. Chest X-ray revealed cardiomegaly, and the electrocardiogram showed diffuse low voltage.
Given the presence of Beck's triad suggestive of cardiac tamponade, a transthoracic echocardiogram was performed, revealing a large pericardial effusion with "swinging heart." A chest CT scan also confirmed the large pericardial effusion.
The diagnosis of cardiac tamponade was made based on the clinical and radiological findings, and pericardial drainage was performed, after which the patient showed clinical improvement.
PCR GenXpert MTB/RIF detected the presence of Mycobacterium tuberculosis on the pericardial fluid, with no resistance to rifampicin. Culture was positive for Mycobacterium tuberculosis.
The diagnosis of tuberculous pericarditis was thus confirmed, and the patient was started on quadruple antituberculosis therapy with good clinical progress.
Single-cell digital twins identify drug targets and repurposable medicine in Alzheimer’s disease
Authors: Ren Yunxiao , Hu Ming , Li Yang E. , Pieper Andrew A. , Cummings Jeffrey , Cheng Feixiong
Published: January 2025

Alzheimer’s disease (AD) is a complex and poorly understood neurodegenerative disorder without sufficiently effective treatments. Novel approaches to identify FDA-approved drugs that may hold potential for mitigating symptoms of AD hold promise for addressing this problem. One such strategy is the use of digital twins (DTs), which are virtual representations of physical entities that facilitate therapeutic target identification by accurately characterizing disease heterogeneities in real time through continuous feedback and dynamic model updates. In this study, we developed a single-cell digital twin (scDT) framework using single-nuclei RNA-seq (1,197,032 nuclei) and ATAC-seq (740,875 nuclei) data from the middle temporal gyrus of 84 donors across 4 degrees of AD neuropathological change (ADNC). We observed differential gene expression for six major cell types intensified at severe ADNC. We also constructed cell type-specific transcription factor (TF)-target gene networks by leveraging peak-to-gene linkages and motif enrichment analyses. By integrating genome-wide association study (GWAS) loci with cell type-specificcis-regulatory DNA elements (CREs), we identified 141 ADNC-associated genes. Using gene set enrichment analysis (GSEA) and network proximity analysis, we identified 13 candidate repurposable drugs that were associated with these ADNC-associated genes. In summary, we constructed a single-cell digital twin (scDT) framework cell type-specific target identification and drug repurposing in AD and other complex diseases if broadly applied.
TUB-010, a novel anti-CD30 antibody-drug conjugate based on Tub-tag technology, widens the therapeutic window by reducing toxicity while maintaining high efficacy
Authors: Gerlach Marcus , Schmitt Saskia , Cyprys Philipp , Kasper Marc-André , Mai Isabelle , Klanova Magdalena , Maiser Andreas , Leonhardt Heinrich , Hackenberger Christian P. R. , Fingerle-Rowson Guenter R. , Vogl Annette M. , Schumacher Dominik , Helma Jonas
Published: January 2025

TUB-010 is a next-generation antibody-drug conjugate (ADC) targeting CD30, which is expressed on various hematopoietic malignancies such as Hodgkin lymphoma and anaplastic large cell lymphoma. Patients with refractory and relapsed CD30-positive cancers often lack effective and tolerable therapy options. Among the therapeutic options for these patients is brentuximab vedotin (Adcetris), a monomethyl auristatin E (MMAE)-delivering anti-CD30 ADC with a mean drug-to antibody ratio (DAR) of 4. Adcetris exhibits a high response rate at the cost of significant toxicities, among which neutropenia and peripheral neuropathy are the most prevalent adverse events, which are likely driven by the payload MMAE and instability of the maleimide conjugation chemistry.

TUB-010 uses the same antibody brentuximab and payload MMAE as Adcetris, but instead of maleimide chemistry, TUB-010 is based on the Tub-tag conjugation strategy, which enables the generation of a homogenous and site-specific DAR 2 ADC with unique biophysical properties. This new technology stably attaches MMAE to the hydrophilic Tub-tag peptides on the light chains via chemoenzymatic conjugation using the enzyme tubulin tyrosine ligase.

TUB-010 demonstrates similar binding affinity, internalization and lysosomal release characteristics as Adcetris in CD30-positive cells. When normalized to the MMAE concentration, TUB-010 shows comparablein vitrocytotoxic efficacy as well as similar bystander activity compared to Adcetris on established cancer cell lines. Importantly, TUB-010 exhibits higher stability with neglectable premature deconjugation in circulation and reduced high molecular weight species formation as well as lower non-specific cytotoxicity on target-negative cells compared to Adcetris. As a consequence, TUB-010 induces superior tumor control compared to Adcetris when dosed at equal MMAE concentrationsin vivoand also shows lower toxicity and higher tolerability in rodents and non-human primates.

Taken together, TUB-010 is a novel and potential best-in-class anti-CD30 ADC with improved biophysical properties designed to deliver the cytotoxic payload with higher precision and with a wider therapeutic window than Adcetris using Tub-tag conjugation technology. Therefore, TUB-010 may increase the clinical benefit of ADC therapies for patients with CD30-positive malignancies.