bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP2A-Tws dephosphorylates Map205, is required for Polo localization to microtubules and promotes cytokinesis in Drosophila
Authors: Guelle Marine , Emond-Fraser Virginie , Archambault Vincent 
Published: December 2024

Abstract
Background
Mitosis and cytokinesis are regulated by reversible phosphorylation events controlled by kinases and phosphatases. Drosophila Polo kinase, like its human ortholog PLK1, plays several roles in this process. Multiple mechanisms contribute to regulate Polo/PLK1 activity, localization and interactions. We previously showed that the microtubule-associated protein Map205 interacts with Polo during interphase and cytokinesis, inhibiting and sequestering Polo on microtubules. During mitosis, phosphorylation of Map205 at a Cyclin-Dependent Kinase site allows Polo to dissociate from Map205, when Polo must fulfill its mitotic functions. How the Polo/Map205 interaction is restored during mitotic exit remained unknown.

Results
Here we show that PP2A-Tws/B55 is required to dephosphorylate Map205, and enables the Map205-dependent localization of Polo to microtubules during cytokinesis. In addition, we show that PP2A-Tws is required for spindle function during cytokinesis, consistent with the essential role of Polo in this process.

Conclusions
These findings complement previous studies to provide an understanding of the full cycle of Polo regulation by Map205, kinases and phosphatases. Our findings have implications for the wider network of cell cycle regulatory circuitry.
Cancer Organoids as reliable disease models to drive clinical development of novel therapies
Authors: Blandino Giovanni , Satchi-Fainaro Ronit , Tinhofer Ingeborg , Tonon Giovanni , Heilshorn Sarah C. , Kwon Yong-Jun , Pestana Ana , Frascolla Carlotta , Pompili Luca , Puce Aurora , Iachettini Sara , Tocci Annalisa , Karkampouna Sofia , Kruithof-de Julio Marianna , Tocci Piera , Porciello Nicla , Maccaroni Klizia , Rutigliano Daniela , Shen Xiling , Ciliberto Gennaro 
Published: December 2024

AbstractOn September 23–24 (2024) the 6th Workshop IRE on Translational Oncology, titled “Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies,” took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells interacting within their microenvironments. These models address critical unmet needs in precision medicine, particularly in aiding clinical decision-making. The rapid development of these human tissue avatars has enabled advanced modeling of cellular alterations in disease states and the screening of compounds to uncover novel therapeutic pathways.Throughout the event, distinguished speakers shared their expertise and research findings, illustrating how organoids are transforming our understanding of treatment resistance, metastatic dynamics, and the interaction between tumors and the surrounding microenvironment.This conference served as a pivotal opportunity to strengthen international collaborations and spark innovative translational approaches. Its goal was to accelerate the shift from preclinical research to clinical application, paving the way for increasingly personalized and effective cancer therapies.
Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial
Authors: Freiberg Jeffrey A. , Siemann Justin K. , Qian Edward T. , Ereshefsky Benjamin J. , Hennessy Cassandra , Stollings Joanna L. , Rali Taylor M. , Harrell Frank E. , Gatto Cheryl L. , Rice Todd W. , Nelson George E. ,   for the Vanderbilt Center for Learning Healthcare
Published: December 2024

Abstract
Background
Vancomycin, an antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial.

Methods
STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. The objective of this study is to test whether the use of MRSA PCR testing can safely reduce inappropriate vancomycin use in an intensive care setting. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the expected number of hours alive and free of the use of vancomycin within the first 7 days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin.

Discussion
STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting.

Trial registration
ClinicalTrials.gov NCT06272994. Registered on February 22, 2024.
Pulmonary infection caused by Tropheryma whipplei: a case report and review of the literature
Authors: Shi Jianglong , Liu Ren , Qiu Jiehui , Wei Chunping , Pan Dejin , Xiang Tianxin , Cheng Na 
Published: December 2024

Abstract
Background
Tropheryma whipplei pneumonia is an infrequent medical condition. The clinical symptoms associated with this disease are nonspecific, often resulting in misdiagnosis or missed diagnosis. Therefore, sharing and summarizing the experiences in the diagnosis and treatment of this disease can deepen global understanding and awareness of it.

Case presentation
The patient is a 78-year-old married Han Chinese female who was admitted to the hospital after experiencing fever, dry cough, and fatigue for 4 days. A lung computed tomography scan revealed inflammatory exudation in the lower left lung, accompanied by pleural effusion. The bronchoalveolar lavage fluid was subjected to further analysis using metagenomic next-generation sequencing, which identified 41 genetic sequences associated with Tropheryma whipplei. Consequently, she was diagnosed with Tropheryma whipplei pneumonia. After initiating treatment with doxycycline and biapenem, the patient’s symptoms showed significant improvement. Upon discharge, the patient continued treatment with a combination of doxycycline and hydroxychloroquine, which was discontinued after 4 days. At 12-month follow-up, the patient reported overall good health, with no symptoms of fever, cough, or any other discomfort.

Conclusion
Tropheryma whipplei pneumonia is a rare condition with nonspecific symptoms. The application of metagenomic next-generation sequencing technology in pulmonary infections helps to rapidly identify rare pathogens, providing a solid foundation for precise and effective antibacterial treatment for patients.
Moringa oleifera products as nutraceuticals for sustainable poultry production
Authors: Egbu Chidozie Freedom , Mulaudzi Anzai , Motsei Lebogang Ezra , Mnisi Caven Mguvane 
Published: December 2024

AbstractMoringa (Moringa oleifera) products hold promise as sources of nutraceuticals in poultry diets due to the presence of proteins, carbohydrates, minerals, vitamins, and polyphenolic compounds with growth-boosting, antimicrobial, and antioxidant activities. Moringa leaves, seeds, or their extracts are among the natural additives that contain polyphenolic substances such as quercetin, catechin, alkaloids, and kaempferol that have been extensively exploited to optimise poultry nutrition. These substances can stimulate fast growth rates, boost the nutritional quality of poultry products, and suppress pathogenic gut microbial proliferation. However, high levels of primary (fibre) and secondary metabolites (tannins, saponins, cyanogenic glycoside, and phytates) in moringa seeds or leaves limit their utilization as nutraceuticals in poultry feeds. Consequently, various conflicting findings have been reported regarding the potential benefits of moringa products in poultry diets. For this review, data from 43 research articles sourced from PubMed, Google Scholar, Web of Science, AGRICOLA, CAB Direct, and Scopus met the inclusion criteria. The review provides an overview of the nutraceutical composition of moringa products and their feeding value in poultry production. The challenges and benefits of adopting moringa products in conventional poultry diets and potential strategies that can enhance their utility in poultry nutrition to warrant a positive impact on food security were discussed. We also delved into the importance of determining optimal dosage levels given that low doses result in limited positive impacts while higher doses may cause debilitating antinutritional effects. We found that tailoring the inclusion dosages based on poultry species, physiological stages, form of moringa products, and bioprocessing techniques can mitigate the impact of antinutrients, thus allowing for higher inclusion rates. Conclusively, the use of moringa nutraceuticals could improve poultry production efficiency and promote food security and sustainable agricultural practices. Policy implications must include establishing clear guidelines for the safe and effective use of moringa products in poultry diets as alternatives to synthetic additives.
AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition
Authors: Kang HyunJun , Valerio Melissa , Feng Jia , Gu Long , Hoang Dinh Hoa , Blackmon Amanda , Sharkas Shawn , Pathak Khyatiben , Jossart Jennifer , Li Zhuo , Zhang Hongyu , Zhang Bin , Pirrotte Patrick , Perry J. Jefferson P. , Hickey Robert J. , Malkas Linda , Marcucci Guido , Nguyen Le Xuan Truong 
Published: December 2024

AbstractCytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 − blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs). In vivo, AOH-treated mice demonstrated prolonged survival compared to controls (50 vs. 35 days; p < 0.0001) with reduced LSC burden, as shown in secondary transplants (42 vs. 30 days, p < 0.0001). Mechanistically, AOH disrupted mitochondrial PCNA’s binding to the OPA1 protein, enhancing OPA1’s interaction with its E3 ligase, MARCH5, which led to OPA1 degradation. This process reduced mitochondrial length, fatty acid oxidation (FAO), and oxidative phosphorylation (OXPHOS), thereby inhibiting LSC expansion. The addition of venetoclax (VEN), an FDA-approved Bcl-2 inhibitor, further enhanced AOH’s effects, reducing mitochondrial length, FAO, and OXPHOS while improving survival in AML models. While VEN is approved for AML, AOH is under clinical investigation for solid tumors, and our findings support its broader therapeutic potential.
Aseismic deformation within fold-and-thrust belts: example from the Tsengwen River section of southwest Taiwan
Authors: Le Béon Maryline , Chen Chang-Chih , Huang Wen-Jeng , Ching Kuo-En , Shih Jhih-Wei , Tseng Ya-Chu , Chiou Yi-Wei , Liu Yen-Chiu , Hsieh Meng-Long , Pathier Erwan , Lu Chih-Heng , Fruneau Bénédicte 
Published: December 2024

AbstractWe report a rarely observed case of steady aseismic deformation in the context of a fold-and-thrust belt, with a well-documented structural and lithological background. We focus on a 12-km-long section across the foothills of southwestern Taiwan, where about 23 mm/yr of westward compression is observed. From west to east, the surface geological structures include an anticline, a thrust and a backthrust. We determine Holocene uplift rates based on fluvial terraces, invert the interseismic 3D velocity field using existing geodetic datasets, and build a geological cross-section to constrain the possible deep geometry for the structure responsible for the observed surface deformation. Geodetic vertical velocities and Holocene uplift rates show a similar pattern, with rates rapidly increasing eastward, then remaining relatively constant across the fold axis and thrust, and finally sharply decreasing across the backthrust, across which InSAR (Interferometric Synthetic Aperture Radar) observations suggest a velocity discontinuity. Our observations show that active deformation is occurring mainly aseismically and involves the anticline and backthrust. Our cross-section illustrates a 4–5 km deep wedge with a passive roof thrust corresponding to the backthrust, on the hanging wall of which the anticline is located. A classical fault-bend fold model with a slip rate of 21 ± 2 mm/yr can explain most of the observations, yet local misfit suggests a possible contribution to uplift from pure shear of clayey rocks in the anticline core. Based on published records from a deep well drilled across the fold core and backthrust, clay-rich lithology and elevated fluid content are likely to favor aseismic slip.
Potential role of electroencephalographic monitoring for diagnosis and treatment of local anesthetic systemic toxicity during general anesthesia: a case report
Authors: Wakabayashi Ryo , Azuma Seiichi , Hayashi Saori , Ueda Yuji , Iwakiri Masaki , Asamoto Masaaki , Uchida Kanji 
Published: December 2024

Abstract
Background
Local anesthetic systemic toxicity (LAST) is a rare but potentially life-threatening complication. Under general anesthesia, neurological signs are often masked, delaying diagnosis and increasing the risk of sudden cardiovascular collapse. Therefore, early detection methods are critically needed.

Case presentation
A 48-year-old male patient (height: 182 cm, weight: 98 kg) underwent resection of a mediastinal goiter. He received 10 mL of 4% lidocaine for topical airway anesthesia and 20 mL of 1% lidocaine with 1:100,000 epinephrine for chest wall anesthesia. Thirty minutes after airway anesthesia, continuous theta waves appeared on the frontal electroencephalogram (EEG), which were enhanced following chest wall anesthesia. These waves transitioned into a repeating pattern and evolved into sharp periodic discharges. After administering 150 mL of 20% lipid emulsion, the EEG normalized.

Conclusions
This case highlights that EEG monitoring during general anesthesia may facilitate the early detection of LAST and provide real-time feedback on treatment efficacy.
Accountability and objectivity: Humanitarian narratives at the intersection of evidence and localisation
Authors: Turner Ellen , Lokot Michelle , Lange Isabelle L. , Wake Caitlin , Roberts Bayard 
Published: December 2024

AbstractIn the last decade, there has been a push for greater evidence-based practice within the humanitarian sector, alongside an increasing turn towards localising humanitarian assistance. Humanitarian actors and organisations have been increasing their production and use of evidence, while also being encouraged to reflect more critically on power hierarchies and decolonise humanitarian aid. This paper explores the intersection of these two narratives, examining how the use of evidence in humanitarian decision-making fits within a localisation agenda. Based on interviews with humanitarian health practitioners located globally, we examine how evidence is defined, and how it is used, including to inform both hierarchical and bottom-up approaches to decision-making. We find clear hierarchies about what counts as good evidence, with a weighting towards randomised-controlled trials, and that the perspectives of populations most affected by crises and the expertise of local actors were not routinely seen as central forms of evidence. Narratives about needing to build the capacity of local actors persist, alongside the notion of evidence as objective. We suggest that a disconnect exists between humanitarian discourses about evidence and localisation, arguing for the need to view evidence as political and influenced by researcher positionality This suggests that more consideration of locally-driven knowledge is needed and will strengthen humanitarian decision-making. We argue that a distinction between evidence and localisation does a disservice to both agendas and that finding synergies between these concepts would strengthen both.
Anticipatory actions: lessons from the storm Ana in Mocuba district, Mozambique
Authors: Popat Meizal , Rathod Komal , Artur Luis , de Perez Erin Coughlan , Sharma Akriti , Beca Noah , Van Sant Carolyn 
Published: December 2024

AbstractIn January 2022, the Mozambique Red Cross provided non-food items to people who were forecasted to be impacted by flooding from the tropical storm Ana in the district of Mocuba, Zambezia province, Mozambique. This was an activation of their anticipatory action protocol, an innovative mechanism for forecast-based action. While anticipatory action is growing rapidly around the world, there is a lack of evidence on the effectiveness of different anticipatory actions across hazards. In this study, we compare reported health outcomes and asset losses from a survey of beneficiaries of an anticipatory action program in Mozambique, implemented by the Mozambique Red Cross. Given the short warning time, Mozambique Red Cross was able to provide non-food items, namely early warning messages, buckets, cups, mosquito nets, soaps, and COVID-19 masks to 855 number of people 24h before the flooding occurred. Using propensity score matching, we did not find statistically significant differences in health outcomes loss of assets or personal documents during the flood event, between beneficiaries and non-beneficiaries (comparison group). The lack of observable statistical differences between the groups could be due to either the late timing of intervention or a lack of tangible utility of the non-food items for the intended objectives. Our findings suggest that early warning and action need to be backed by proper and timely logistical and organizational investments and tailored to local contexts if they are to bear significant results. Further investment in anticipatory action systems should ensure that actors have the infrastructure and personnel ready to act quickly enough based on the forecast.
Designing a humanitarian relief logistics network considering the cost of deprivation using a robust-fuzzy-probabilistic planning method
Authors: Ghahremani-Nahr Javid , Nozari Hamed , Szmelter-Jarosz Agnieszka 
Published: December 2024

AbstractThis study addresses deprivation costs in humanitarian logistics by incorporating direct and indirect impacts into a robust-fuzzy-probabilistic framework to optimize resource allocation and minimize delays in disaster response. This model has concepts such as facility location and optimal flow allocation. The results show that with the increase in the uncertainty rate and as a result of the increase in the number of people affected by the accident and the demand for relief items at the scene of the accident, the costs related to the supply and transportation of the items and the injured have increased. Also, by examining the effect of deprivation cost on the results of the model, it was observed that with the increase of deprivation cost, the model aims to increase the goods transferred to satisfy the demand fully. Therefore, the expenses related to deprivation have decreased, but on the other hand, the costs associated with the transfer of products have increased. As a result, the cost of the entire relief logistics network has increased. Finally, by examining the effects of the weighting coefficient of the objective function on the values of the objective function of the problem, it can be seen that with the increase of this weighting coefficient, the value of the objective function has increased due to the increase in the volume of transfers of relief items.
INI1 (SMARCB1) deletion of lung cancer: a case report and literature review
Authors: Ma Hong-Yan , Shi Shuai , Sang Yin Zhou , Sun Jie , Wang Xing-guang , Zhang Zhi-Gang 
Published: December 2024

Abstract
Background
Integrase interaction factor 1 (INI1), also known as switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), is a tumor suppressor gene. The INI1 protein is widely expressed in normal cell nuclei. This case report described a series of lung adenocarcinomas with deletion of the INI1 gene.

Case presentation
The patient, a 65-year-old female, underwent lung biopsy surgery at our hospital in April 2023. The tumor tissue was stained with immunohistochemistry and ultimately diagnosed as INI1-deficient lung adenocarcinoma. Lack of expression of the INI1 gene has been relatively rare in lung cancer. The INI1 (SMARCB1) protein is a subunit of the SWI/SNF chromatin remodeling complex. Undifferentiated cancers with missing SWI/SNF complexes have been demonstrated to be associated with poor sensitivity to traditional chemotherapy drugs and a poor prognosis. However, histone methyltransferase inhibitors may be effective in treating this tumor.

Conclusions
The purpose of our report was to enhance the understanding of this tumor among clinical and pathological doctors.
Endometriosis - A Medical Challenge: Impact on Fertility and Treatment Method
Authors: Zwierzchowska Maria , Stachowiak Julia , Sosin Julia , Pilarz Anna , Sojka Aleksandra , Salamon Dariusz , Domagała Wojciech 
Published: December 2024

Aim of study:
The subject of this review is to highlight the complexity of the disease known as endometriosis. This disease affects 10% of women of reproductive age, causing a number of symptoms of various origins, and additionally affects women’s fertility, mental health and role in society. The work aims to systematize knowledge about endometriosis, the mechanism by which it affects fertility and possible therapies, including surgical methods and assisted reproductive technology (ART.). The issue of infertility associated with endometriosis is has not been fully explored yet. A personalized treatment plan including medication, surgical assisted reproductive techniques and psychological support should be developed to improve the quality of life of patients with endometriosis and enable them to become pregnant.
Material and methods:
A systematic review of scientific and medical literature from the PubMed and Google Scholar databases was conducted.

Results:
Currently, the most effective treatment for infertility is in vitro fertilization (IVF). Successful treatment of endometriosis-related infertility should be discussed in detail with each patient and the decision on the therapy plan should be individual and comprehensive.
Keywords: endometriosis, infertility, chronic pelvic pain, gynecology, IVF, IVI