bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifungal stewardship in the UK: where are we now?
Authors: Schelenz Silke , Agrawal Samir , Brady Aaron , Kiely Gillian , Riaz Zeshan , Howes Emilie , Felton Tim , Micallef Christianne , Tyler Netta , Bicanic Tihana , White P Lewis 
Published: December 2024

Abstract

Background
Antifungal stewardship (AFS) is the judicious use of today’s antifungal agents with the aim of improving patient outcomes and preserving their future effectiveness. Antifungal resistance (AFR) is increasing globally, with more patients at risk of Invasive Fungal Disease (IFD), highlighting the urgent need to standardize AFS practices in the UK. The aim of this position paper is to understand the current AFS landscape in the UK.

Methods
A virtual panel discussion was held from September to October 2023 on an online platform followed by a virtual meeting with nine healthcare professionals from across the UK selected for their expertise on IFD management and AFS. The discussion was structured across four topics: current AFS landscape, key elements of an AFS programme, diagnostics and diagnostic stewardship, and unmet needs in education and training. A thematic analysis was carried out. The results represent the collated and summarized views from these activities.

Results and discussion
Participants reported barriers to implementing AFS and its integration within antimicrobial stewardship (AMS) programmes in the UK. The primary challenge identified was a lack of resources, including funding and staff time. Sub-optimal fungal diagnostics and limited mycology expertise was reported as a barrier to AFS, clinical IFD and AFR surveillance. Approaches to combatting these challenges may include investing in formal mycology networks to serve as centres of clinical expertise and diagnostic hubs.

Conclusion
National standards for AFS services and associated outcome metrics need to be established to set a benchmark for centres to improve AFS.
Implementing an inclusive digital health ecosystem for healthy aging: a case study on project SingaporeWALK
Authors: Lee Edmund Wei Jian , Bao Huanyu , Singh Navrag B , Pai Sai G S , Pham Ben Tan Phat , Meena Siva Subramaniam Sowmiya , Theng Yin-Leng 
Published: December 2024

Abstract

Objective
To pilot a digital health technologies ecosystem known as project SingaporeWALK (Wearables and Apps for Community Living and Knowledge) that build capacity in older adults, senior center managers, health coaches, and caregivers in using health technologies (eg, wearables, apps, exergames) collaboratively in a gamified way for active aging.

Materials and Methods
The SingaporeWALK ecosystem was set up through 3 initiatives: (1) co-developing technologies with stakeholders; (2) raising digital literacy and capacity building; and (3) cultivating community and intergenerational bonding for active aging through gamified technology use.

Results
Significant improvements in older adults’ self-reported physical and mental health post-intervention were observed.

Discussion
The SingaporeWALK project demonstrated that digital health technologies, when designed with inclusivity and community engagement, could significantly empower active aging.

Conclusion
This project underscored the necessity of a collective and community-centered approach to maximize the efficacy of digital health technologies to support older adults in active aging globally.
Managed honeybees and soil nitrogen availability interactively modulate sunflower production in intensive agricultural landscapes of China
Authors: Wu Panlong , Zhao Yi , Yang Jinyi , Wu Keyuan , Bai Jinrui 
Published: December 2024

Abstract
Insects provide important pollination services for cops. While land use intensification has resulted in steep declines of wild pollinator diversity across agricultural landscapes, releasing managed honeybees has been proposed as a countermeasure. However, it remains uncertain whether managed honeybees can close the pollination gap of sunflower (Helianthus annuus L. [Asterales: Asteraceae]) in areas lacking wild pollinators, and how the benefits of honeybees to sunflower production are modulated by soil nutrients. We investigated the effects of 3 pollination treatments (open, self and hand pollination) on sunflower yield parameters. We also estimated the pollination efficiency of managed honeybees (Apis mellifera L. [Hymenoptera: Apidae]), and analyzed the effects of honeybee visitation and soil nitrogen on sunflower yield parameters. Insect pollinators contributed 73% of seed set and 69% of the weight of filled seeds per head in the open pollination of sunflowers, but large pollination deficits still existed. Insect pollination may enhance sunflower yield by augmenting the number and weight of filled seeds per head, but not by altering the total number of seeds. Except for the total number of seeds per head, yield parameters increased significantly with the number of honeybee visits. Low nitrogen accelerated the positive effect of honeybee pollination on sunflowers, and alleviated the negative effect of distance of beehives on honeybee visitation rate. We conclude that managed honeybees could be used to pollinate sunflowers in areas with the shortage of wild pollinators, and sunflower production may benefit from shortening the distance of beehives and lowing of nitrogen fertilizer inputs.
A method for screening functional anti-Treg antibodies using a Treg-like cell line
Authors: Pfeffer Kirsten , Ho Thai H , Ruiz Yvette , Lake Douglas F 
Published: December 2024

Abstract
Regulatory T cells can suppress activated T cell proliferation by direct cell-contact, although the exact mechanism is poorly understood. Identification of a Treg-specific cell surface molecule that mediates suppression would offer a unique target for cancer immunotherapy to inhibit Treg immunosuppressive function or deplete Tregs in the tumor microenvironment. In this study, we explored a method of whole cell immunization using a Treg-like cell line (MoT cells) to generate and screen monoclonal antibodies that bound cell surface proteins in their native conformations and functionally reversed Treg-mediated suppression. From the 105 hybridomas that bound to the MoT cell surface, a functional screen utilizing conventional Treg suppression assays revealed 32 candidate antibodies that exhibited functional activity (reversed or enhanced suppressive activity). As an example, we characterized one anti-MoT mAb, 12E7, that exhibited strong binding to MoT cells and conventional Treg cell surfaces. This candidate antibody was subsequently found to bind to a potential suppressive target, CD44, and demonstrated the ability to partially reverse MoT and conventional human Treg-mediated suppression.
FCN4Flare: fully convolution neural networks for flare detection
Authors: Jia Minghui , Luo A-Li , Qiu Bo 
Published: December 2024

ABSTRACT
Stellar flares offer invaluable insights into stellar magnetic activity and exoplanetary environments. Automated flare detection enables exploiting vast photometric data sets from missions like Kepler. This paper presents FCN4Flare, a deep learning approach using fully convolutional networks (FCN) for precise point-to-point flare prediction regardless of light-curve length. Key innovations include the NaN Mask to handle missing data automatedly, and the Mask Dice loss to mitigate severe class imbalance. Experimental results show that FCN4Flare significantly outperforms previous methods, achieving a Dice coefficient of 0.64 compared to the state-of-the-art of 0.12. Applying FCN4Flare to Kepler-LAMOST data, we compile a catalogue of 30 285 high-confidence flares across 1426 stars. Flare energies are estimated and stellar/exoplanet properties analysed, identifying pronounced activity for an M-dwarf hosting a habitable zone planet. This work overcomes limitations of prior flare detection methods via deep learning, enabling new scientific discoveries through analysis of photometric time-series data. Code is available at https://github.com/NAOC-LAMOST/fcn4flare
Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing
Authors: Fendler Nikole L , Ly Jimmy , Welp Luisa , Lu Dan , Schulte Fabian , Urlaub Henning , Vos Seychelle M 
Published: December 2024

Abstract
The eukaryotic microrchidia (MORC) protein family are DNA gyrase, Hsp90, histidine kinase, MutL (GHKL)-type ATPases involved in gene expression regulation and chromatin compaction. The molecular mechanisms underlying these activities are incompletely understood. Here, we studied the full-length human MORC2 protein biochemically. We identified a DNA binding site in the C-terminus of the protein, and we observe that this region can be phosphorylated in cells. DNA binding by MORC2 reduces its ATPase activity and MORC2 can entrap multiple DNA substrates between its N-terminal GHKL and C-terminal coiled coil 3 dimerization domains. Finally, we observe that the MORC2 C-terminal DNA binding region is required for gene silencing in cells. Together, our data provide a model to understand how MORC2 engages with DNA substrates to mediate gene silencing.
Novel anti-HER2 ADCs vs dual anti-HER2 antibody for HER2-positive metastatic breast cancer failed to tyrosine kinase inhibitor
Authors: Li Feng , Li Jianbin , Ji Chenchen , Wu Song , Zhang Shaohua , Wang Tao , Bian Li , Jiang Zefei 
Published: December 2024

Abstract

Background
Both novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) and pertuzumab and trastuzumab (HP) combined with chemotherapy(C) regimens are the choice of treatment for HER2 positive metastatic breast cancer (MBC) after tyrosine kinase inhibitors (TKIs). Our team’s previous research has shown significant therapeutic effects of novel anti-HER2 ADCs in patients with TKIs treatment failure. Unfortunately, there is currently no data available to compare novel anti-HER2 ADCs with HP combined with chemotherapy regimens. This study was conducted to compare the efficacy and safety of novel anti-HER2 ADCs with that of the HP combined with chemotherapy regimen in patients for whom TKI treatment failed.

Materials and methods
HER2-positive MBC who used novel anti-HER2 ADCs and HP combined with a chemotherapy regimen from January 2019 to August 2023 were included, and all patients received TKIs. The primary study endpoint was progression-free survival (PFS), while the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results
A total of 150 patients, of which 83 are in the novel anti-HER2 ADCs group and 67 are in the HP combined with chemotherapy. Among these novel anti-HER2 ADCs, 36 patients received treatment with trastuzumab deruxtecan (T-Dxd), and 47 patients received treatment with other new types of ADCs. The median PFS of the novel anti-HER2 ADCs group and HP combined with the chemotherapy group were 7.0 months and 8.9 months, respectively, with ORR of 51.8% and 26.9%, and CBR of 69.9% and 65.7%, respectively. In subgroup, patients receiving T-Dxd showed improvement in PFS compared to the HP combined with chemotherapy group. The most common grade 3-4 adverse events in the novel anti-HER2 ADCs group and the HP combined with chemotherapy group were neutropenia and gastrointestinal symptoms.

Conclusions
In HER2-positive MBC for whom TKI treatment has failed, novel anti-HER2 ADCs and the HP combined with chemotherapy regimen both showed moderate efficacy and tolerable toxicity. Novel anti-HER2 ADCs are the preferred treatment recommendation for TKI failure patients. Meanwhile, based on the results of this study, the HP combined with chemotherapy regimen may also be an option, especially for patients with low accessibility.
Current perspectives on the dynamic culture of mesenchymal stromal/stem cell spheroids
Authors: Ohori-Morita Yumi , Ashry Amal , Niibe Kunimichi , Egusa Hiroshi 
Published: December 2024

Abstract
Mesenchymal stromal/stem cells (MSCs) are promising candidates for regenerative medicine owing to their self-renewal properties, multilineage differentiation, immunomodulatory effects, and angiogenic potential. MSC spheroids fabricated by 3D culture have recently shown enhanced therapeutic potential. MSC spheroids create a specialized niche with tight cell-cell and cell-extracellular matrix interactions, optimizing their cellular function by mimicking the in vivo environment. Methods for 3D cultivation of MSCs can be classified into 2 main forms: static suspension culture and dynamic suspension culture. Numerous studies have reported the beneficial influence of these methods on MSCs, which is displayed by increased differentiation, angiogenic, immunomodulatory, and anti-apoptotic effects, and stemness of MSC spheroids. Particularly, recent studies highlighted the benefits of dynamic suspension cultures of the MSC spheroids in terms of faster and more compact spheroid formation and the long-term maintenance of stemness properties. However, only a few studies have compared the behavior of MSC spheroids formed using static and dynamic suspension cultures, considering the significant differences between their culture conditions. This review summarizes the differences between static and dynamic suspension culture methods and discusses the biological outcomes of MSC spheroids reported in the literature. In particular, we highlight the advantages of the dynamic suspension culture of MSC spheroids and contemplate its future applications for various diseases.
Direct Induction of Buprenorphine Extended-Release: A Case Report
Authors: Azar Pouya , Wong James S.H. , Machado Jessica , Nikoo Mohammadali , Li Victor W. , Ignaszewski Martha J. , Mathew Nickie , Krausz Reinhard M. , Herring Andrew A. , Mullen Rodney , Montaner Julio S.G. , Maharaj Anil R. 
Published: December 2024

Abstract
Buprenorphine has superior safety in opioid use disorder compared with alternatives due to its action as a partial opioid agonist, which limits its ability to cause respiratory depression. There is a risk of precipitated opioid withdrawal after buprenorphine exposure in someone using full opioid agonists. Buprenorphine induction strategies that avoid precipitated withdrawal remain a crucial component for starting buprenorphine in individuals actively using opioids. These strategies start with low doses of buprenorphine increasing over time, which may avoid precipitated withdrawal at the cost of an extended initiation period, potentially discouraging patients and increasing healthcare costs.
A 55-year-old male with severe opioid use disorder and unregulated fentanyl use presented after an overdose, was admitted due to a cerebral venous sinus thrombosis and anemia (hemoglobin of 4.4 g/dL), and was given 300 mg of buprenorphine injection depot subcutaneously without any prior buprenorphine stabilization. Prior to injection, he was taking 30 mg of methadone and 96 mg of oral hydromorphone equivalents daily. Over the 6 hours after injection, he received another 272 mg oral hydromorphone equivalents and experienced a maximum Clinical Opiate Withdrawal Scale score of 7. Over the next 18 hours, he received no additional hydromorphone, and his Clinical Opiate Withdrawal Scale was a maximum of 1.
This case illustrates a buprenorphine induction method without precipitated withdrawal by relying on the elution of buprenorphine from the subcutaneous depot alongside full agonist opioids that are given as needed. If these results are readily replicable, this approach may have significant implications for the accessibility and acceptability of buprenorphine for patients and providers.
Hyperacusis and Tinnitus in Vestibular Migraine Patients
Authors: Haro-Hernandez Elisheba , Perez-Carpena Patricia , Di Berardino Federica , Lopez-Escamez Jose Antonio 
Published: December 2024

Objectives:
To estimate the prevalence of tinnitus and hyperacusis in patients with vestibular migraine (VM), and to define the association with hearing loss, anxiety, and depression.

Design:
A cross-sectional, multicenter study including 51 adult patients with definite or probable VM, defined according to the Barany Society diagnostic criteria. Audiological examinations were performed by pure tones extended to high frequencies to assess hearing thresholds. Psychoacoustic (pitch, masking level, and residual inhibition) and psychometric assessment of tinnitus was performed in all patients that reported tinnitus with the following questionnaires: Tinnitus Handicap Inventory (THI), Hypersensitivity to Sound Questionnaire and Hospital Anxiety Depression Scale. Correlation and regression analyses were used to assess the relationship between THI scores hyperacusis, anxiety, and depression in patients with VM.

Results:
Forty-five of 50 VM patients (90%) were females; 38 out of 50 (75%) patients reported tinnitus. In our series, the most common frequency (pitch) for tinnitus was 8000 Hz. Tinnitus was not associated with hearing loss in patients with VM and the hearing thresholds were similar in VM patients with or without tinnitus. Hyperacusis was reported in 35 (60%) individuals, and in patients with tinnitus, the THI scores were associated with higher scores in Hypersensitivity to Sound Questionnaire, and anxiety and depression subscales of Hospital Anxiety Depression Scale. There were differences in the distribution of hearing loss in patients with hyperacusis, however both groups did not exceed the normal hearing threshold (17.18 ± 13.43 patients with hyperacusis and 11.66 ± 5.41, p = 0.023 in patients without hyperacusis).

Conclusions:
Tinnitus is a common symptom in patients with VM and it is not related to hearing loss in the standard audiogram. Hyperacusis was associated with tinnitus, anxiety, and depression, but it was not associated with hearing thresholds.
Successful Treatment of Primary Acanthamoeba Cutis in a Patient With Chronic Lymphocytic Leukemia on Acalabrutinib
Authors: Erem Anna Sarah , McAllister Josephine Chu , Quattrochi Brian , Gru Alejandro A. 
Published: December 2024

Abstract:
Primary cutaneous amoebiasis is rare, and typically affects immunocompromised patients and presents with unique clinical and histopathologic changes. Untreated, the infection could progress to involve the central nervous system, which is almost universally fatal. We present a case of primary cutaneous acanthamoebiasis in a patient with chronic lymphocytic leukemia on acalabrutinib. Timely diagnosis and treatment resulted in complete resolution of lesions and a disease-free status at the 14-month follow-up. A 76-year-old man presented with a 2-month history of multiple, nonhealing, ulcerated, erythematous, painful, crusted nodules on his trunk, and upper and lower extremities. Two punch biopsies showed mixed inflammatory infiltrate with a histiocytic reaction and microabscesses extending into the deep dermis. Rare, unusual structures with cytoplasmic vacuolations and round nuclei were seen on repeated biopsies. Gomori methenamine silver delineated wrinkled double-walled cytoplasm of rare parasites, concerning for amoebic infection. Molecular workup (polymerase chain reaction) came back positive for Acanthamoeba castellanii. Initial treatment involved flucytosine and fluconazole, followed by fluconazole and miltefosine, but both were discontinued because of nausea and replaced with single-agent voriconazole. Acanthamoeba cutis poses unique diagnostic challenges in a setting of novel agents for chronic lymphocytic leukemia and may be underrecognized. With the expanding population of immunocompromised patients, rare cutaneous infections should enter the differential early on along with early consideration of molecular ancillary testing. The long-term immunomodulating properties of acalabrutinib remain to be elucidated.
Histopathologic Comparison Among Drug Eruptions Induced by Enfortumab Vedotin, Brentuximab Vedotin, and Taxanes
Authors: Iwahashi Yoshifumi , Goto Keisuke , Ohe Shuichi , Bun Shota , Kido Kansuke , Matsui Takahiro , Morii Eiichi , Honma Keiichiro 
Published: December 2024

Abstract:
Microtubule-stabilizing agents (enfortumab vedotin and brentuximab vedotin) and microtubule-disrupting agents (docetaxel and paclitaxel) are used as anticancer agents but can also induce drug eruptions. Recently, mitotic arrest figures have been reported in various non-neoplastic cells as the histopathologic side effect of these drug eruptions. Therefore, we performed a comparative analysis of drug eruptions associated with these microtubule-targeting agents. Enfortumab vedotin-, brentuximab vedotin-, docetaxel-, and paclitaxel-associated drug eruptions were retrieved from 4 hospitals in 5, 5, 5, and 7 patients, respectively. Ring mitotic and other mitotic arrest figures were observed in the epidermis in all types of drug eruption but were most frequently (100%) observed in enfortumab vedotin-induced eruptions. Such a finding was also occasionally observed in the sweat ductoglandular units but not in the follicular epithelium. Keratinocyte multinucleation and apoptotic keratinocytes distributed predominantly in the upper part of the epidermis were also observed in these eruptions, particularly in enfortumab vedotin-induced eruptions (4/5, 80%). In conclusion, drug eruptions associated with microtubule-targeting agents, particularly enfortumab vedotin, can often exhibit mitotic arrest figures, keratinocyte multinucleation, and apoptotic keratinocytes predominantly observed in the upper part of the epidermis. These characteristic histopathologic features can be the diagnostic clues of drug eruptions induced by microtubule-targeting agents.
Clinical significance of the albumin-to-globulin ratio in overweight or obese elderly patients with cancer: A multicenter observational study
Authors: Zhang Xi , Dai Xiang-Ting , Huang Jia-Xin , Tang Meng , Shi Han-Ping , Cong Ming-Hua 
Published: December 2024

Abstract

Background
Elderly patients with cancer who are overweight or obese tend to show signs of inflammation or malnutrition. The albumin-to-globulin ratio (AGR) is a clinical indicator of the nutritional status and presence of systemic inflammation in cancer patients. However, its predictive value in this specific population has not yet been elucidated.

Methods
This study, comprising 917 overweight or obese elderly cancer patients, was conducted as a multicenter clinical trial. The relationship between the AGR and survival outcome was assessed using Kaplan-Meier survival curve analyses and the Cox regression model for HRs. Additionally, the prognostic value of the pretreatment AGR was validated by performing a propensity score matching analysis.

Results
The optimal cutoff value for a low AGR was 1.25. A notable decrease in the risk of all-cause mortality was observed with each increase in the AGR value. Specifically, for every SD increase, the HR was 0.83 (95% CI: 0.74–0.93, P = 0.001). After adjustment, it was determined that a decreased AGR was independently linked to a worse prognosis among elderly cancer patients who were overweight or obese (HR: 1.79, 95% CI: 1.40–2.27, P < 0.001). In addition, a reduced AGR is correlated with poorer outcomes in the context of certain malignancies, particularly lung, upper gastrointestinal, and colorectal malignancies. Notably, the effect of the AGR on the overall survival was influenced by the Eastern Cooperative Oncology Group performance status. The validity of our primary findings was confirmed through a propensity score matching analysis, which accounted for potential confounding factors.

Conclusions
A reduced AGR is linked to a poor prognosis, particularly when concurrent with a poor Eastern Cooperative Oncology Group performance status in overweight or obese elderly cancer patients.