bluuebunny/crossref_metadata_2025 huggingface dataset:
Polinômios e números primos: explorando padrões através de cálculos computacionais e a Conjectura 41
Authors: Avila Jorge Andrés Julca , Tostes Éder Luis , Andrade Gabriel Silva de
Published: December 2024

Hardy e Littlewood, ao longo de suas notáveis carreiras, propuseram várias conjecturas matemáticas. Em particular, a Conjectura F de Hardy-Littlewood, formulada em 1922, sugere que certas funções quadráticas geram infinitos números primos e estabelece uma relação assintótica para a função de contagem de números primos. Este trabalho apresenta um polinômio de segundo grau, v41(x)=x2+81x+412, derivado do n-quadrado Zeta, que representa uma aplicação específica da Conjectura F. Propomos, portanto, uma abordagem alternativa para a demonstração da Conjectura F através da Conjectura 41. "A Conjectura 41 postula que ``A função de contagem de primos-41, gerada pelo polinômio v41(x), é assintoticamente igual a x/(Alnx + B)". Adicionalmente, constatamos que, se a Conjectura 41 for verdadeira, o polinômio em questão gerará infinitos números primos.
The Application of i-Tasser and related studies to predict the full-length structure, thermodynamic states and functional analysis of the Kirsten Rat Sarcoma Virus (KRAS) protein; An observation of KRAS structural and functional integrity.
Authors: Kadir SDanish , Chowdhury Tanvir , Saha Mrinal Kranti , Laskar Partha
Published: December 2024

KRAS (Kirsten Rat Sarcoma Virus) is a Ras (Rat Sarcoma virus) family homologous. Due to its structural characteristics and biochemical properties, it’s been regarded as one of the most common drivers in various cellular signaling pathways. Due to its biochemical and pharmacological importance, KRAS been regarded as the “Holy Grail” of drug discovery. To understand the structure and thermodynamics of this protein, we tried to focus on the confirmational and functional portion of this specific protein. “i-Tesser” is applied to predict the structure of KRAS. A prediction for the secondary and full-length 3D structure been developed. Additional generation of the B factor value, Solvent accessibility, ligand bonded structure, as well as the 5 different thermodynamic state models of the KRAS and their functions are analyzed. The primary, metastable, ligand-bounded reactive states are visualized with the additional application of NAMD (Nanoscale Molecular Dynamics) and VMD (Visualization Molecular Dynamics). The drawn models showcase a C score value ranging between (-0.02 to -1.45) and Cluster density (0.0683 to 0.2835), along with a standard deviation value of (0.704983). Predicted secondary, 3D, and Thermodynamic models are drawn and supported by modeling their Solvent accessibility and B factor values. The 5 different models and the related structural and functional analysis provide additional information about the stability of KRAS structure and its function.
Short-term clinical study on changes in bone mass around the implant following touch-controlled, minimally invasive implantation in the mandibular first molar region based on CBCT imaging
Authors: Li Wenchao , Ruan Ning , Tian Yuan , Li Senhao , Han Weize , Zhang Xinxin , Yu Haoyang , Xie Yu
Published: December 2024

This study was aimed to investigate the change of peri-implant bone mass after touch-controlled, minimally invasive implantationin mandibular first molar region by CBCT. This retrospective study was conducted, involving 60 implants mandibular first molar implant repairation. Touch-controlled, minimally invasive implantation was performed, and healing abutments were installed post-surgery. CBCT scans were obtained at four time points: on the day of surgery (T0), 1 month post-surgery (T1), 3 months (T2), and 6 months (T3). Implant retention was calculated. Measuring horizontal and vertical bone absorption at each time point, both bucco-lingually and in the proximal and distal regions. The implant retention at T3 was 100%. Bone resorption was observed at the proximal and distal sites of the implant as early as T1, with more noticeable resorption at T2 and T3. Compared to T1, there was a significant increase in bone resorption, and the resorption amount tended to stabilize by T3. Horizontal bone resorption was not evident. In a word, Following touch-controlled, minimally invasive implantation of mandibular first molars, peri-implant vertical bone resorption was observed in the proximal, distal, and bucco-lingual regions, while horizontal bone resorption was not apparent. These findings provide valuable guidance for implant clinicians in selecting optimal surgical techniques.
Progress in ubiquitination and hepatocellular carcinoma: A bibliometric analysis
Authors: Li Ming , Xu Zhiliang , Liang Siqin , Lv Qiaoli , You Xiaoxiang , Yuan Tinghao , He Jun , Tu Qiang
Published: December 2024

Background and Purpose Ubiquitination modifications can affect hepatocellular carcinoma (HCC) progression through various signaling pathways. However, no significant results have been observed regarding protein ubiquitination in HCC’s therapeutic transformation. This study aimed to explore the research areas related to ubiquitination and HCC from a bibliometric perspective.Methods Articles and reviews on HCC and ubiquitination published between 2000 and 2023 were obtained from the Web of Science Core Collection (WOSCC). CiteSpace, VOSviewer, and R-bibliometrix were used for the bibliometric and visualization analyses.Results Altogether, 358 papers on ubiquitination and HCC were extracted from the WOSCC. Over 24 years, the number of publications has increased. Since the beginning of 2019, studies related to this topic have increased significantly, indicating that the role of ubiquitination modification in HCC is currently popular. China is the leading country in this field with the largest number of publications. The Chinese Academy of Sciences is one of the most influential institutions. Qiao, Yongxia, and Zhang Jie are highly productive authors with major achievements. The journal Cell Death & Disease had the highest number of publications, and the most highly cited journal was Oncogene. The highest citation burst intensity was Sung (2021). In the keyword strategy map, “cancer antigens” are popular keywords in HCC and ubiquitination research.Conclusion A comprehensive visual analysis of ubiquitination and HCC research was conducted using bibliometric methods, showing the publications and popular topics in this field over the past two decades, thus providing references for the future direction of ubiquitination and HCC research.
Nurses’ and midwives’ job satisfaction and retention during COVID-19: A scoping review.
Authors: Hynes Laura , Geraghty Sadie , McChlery Sheena , Smyth Aisling , Brar Reeti , Clark-Burg Karen
Published: December 2024

Background: The COVID-19 pandemic focused attention on the previously well-documented world-wide shortage of nurses and midwives. The pandemic accentuated this crisis, which resulted in nurses and midwives questioning their roles and their careers. The impact of the pandemic on job satisfaction and the intention of nurses and midwives to stay has not been adequately explored.
Aim: The aim of this scoping review was to identify and map the literature that describes the intrinsic and extrinsic factors that influenced nurses’ and midwives’ job satisfaction and intent to stay or leave their employment or profession during the COVID-19 pandemic.
Method: This scoping review was conducted according to the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) and the Joanna Briggs Institute (JBI) guidelines. Studies written in English and published between 2019 and December 2023 were included, and consisted of quantitative, qualitative and mixed methods studies. MEDLINE CINAHL, and PsychINFO were the key information sources. The search terms for this review were developed using the PCC mnemonic: Participants, Concepts and Context. The JBI approach to sources selection, data extraction and presentation of data was used.
Results: A total of 1833 relevant articles were identified. Of these, 17 articles met the inclusion criteria. Eleven factors were identified as impacting on nurses and midwives job satisfaction and retention during the COVID19 pandemic.
Conclusion: The findings reveal key factors, such as patient acuity, staffing dynamics, leadership quality, and resource availability, have significantly shaped the professional experiences of nurses and midwives during the pandemic.
ATR-FTIR spectroscopic markers indicating drug resistance in selected Candida strains
Authors: Dróżdż Agnieszka , Kubera Dominika , Olender Alina , Dabrowski Wojciech , Szukala Magdalena , Wosko Sylwia , Chwiej Joanna , Rugiel Marzena , Kawoń Kamil , Gagoś Mariusz
Published: December 2024

The rising incidence of fungal infections and the increasing prevalence of antifungal resistance highlight the need for rapid and reliable diagnostic methods. This study investigates the potential of ATR-FTIR spectroscopy to identify spectroscopic markers of drug resistance in selected Candida strains. In this pilot study, ATR-FTIR spectroscopy was employed to analyse the biochemical composition of Candida albicans, Candida glabrata, and Candida dubliniensis isolates. The minimum inhibitory concentrations (MIC) of antibiotics were determined using antibiotic concentration gradient strips, and the spectral data were processed to identify differences between resistant and sensitive isolates. Based on the results for Candida albicans, Candida glabrata, and Candida dubliniensis, specific ATR-FITR spectroscopic markers of drug resistance were identified, highlighting the necessity for these markers to be antibiotic-specific. Despite the study's limitations the findings underscore the potential of ATR-FTIR spectroscopy in identifying spectroscopic markers of antifungal resistance. These preliminary results provide a foundation for further research, which could lead to the development of rapid diagnostic tools for detecting drug-resistant Candida strains, thereby improving the management and treatment of fungal infections.
High temperature effects on maize photosynthesis during stress and recovery phase at the seed setting stage
Authors: Teng Li , Qing Liu , Shumei Wang , Xuepeng Zhang , Yuanquan Chen , Wangsheng Gao , Peng Sui
Published: December 2024

With the climate change, high temperature (HT) stress will have more serious impacts on maize production. Photosynthesis is the basis of crop yield, which is also sensitive to HT. HT effects are not only occurred during the stress periods, but also lasted after the stress is lifted, but with few attention. To explore the maize photosynthesis after HT removal, two maize varieties with different heat sensitivity (Jinhai 5 (JH) in 2021; JH and Xianyu 335 (XY) in 2022) were exposed to HT using the pot experiment. Photosynthesis and relevant physiological indicators were measured during stress and recovery phase. Results showed that at the ending of HT, maize photosynthesis was significantly inhibited in the two years. Photosynthesis of JH was not recovery at 2 d and 3 d after HT removal in 2021 and 2022, which was 23.8% and 14.7% lower than control. For XY, the photosynthesis was 11.2% lower than control at 5 d after HT removal in 2022. Chlorophyll fluorescence parameters were significantly changed during HT periods. The lasting effects were not showed in JH, but occurred in XY. Malondialdehyde (MDA), peroxidase (POD) and superoxide dismutase (SOD) increased by 49.5%, 21.6% and 36.8% under HT, and accumulation were also found at the 2 d after HT removal, with much higher for POD and SOD (38.3% and 40.1%). Meanwhile, the arrangement and morphology of chloroplasts in mesophyll cells significantly changed, and even could not recover at 4 d after HT removal. Finally, HT stress caused significant yield penalty on maize.
2D Basement Relief Inversion using Sparse Regularization
Authors: Barboza Francisco Márcio , Silva Anthony da Cunha Romão E , Carvalho Bruno M.
Published: December 2024

Basement relief gravimetry is crucial in geophysics, especially for oil exploration and mineral prospecting. It addresses an inverse geophysical problem, where geological model parameters—depths of constant-density prisms representing the basement relief—are inferred from gravitational anomaly data. These problems are often ill-posed, meaning small data changes can cause significant solution variations. To counter this, regularization techniques, such as Tikhonov's method, are used to stabilize solutions. This study compares several regularization techniques applied to gravimetric inversion, including Smoothness Constraints, Total Variation, the Discrete Cosine Transform (DCT), and the Discrete Wavelet Transform (DWT) with Daubechies D4 wavelets. Optimization methods, like the Genetic Algorithm (GA), are employed to minimize the objective function and find optimal prism depths. GA, inspired by natural selection, iteratively selects the best solutions to minimize the objective function. The analysis shows that all regularization techniques and the GA are effective, with Smoothness Constraints being the most effective for synthetic models. For real-data models, all methods performed similarly.
Endovascular Transcatheter Photodynamic Ablation to Downstage Locally Advanced Pancreatic Cancer Followed by Surgery: A Proof-of-Concept Study in a Porcine Model
Authors: Vazquez Alain Garcia , Saeidi Tina , Verde Juan , Wanert Fanélie , Spiridon Irene Alexandra , Schmid Axel , Swanstrom Lee , Lilge Lothar , Bogaards Arjen
Published: December 2024

Background
Pancreatic cancers can involve large intrapancreatic blood vessels early, making complete tumour resection technically challenging or impossible for surgeons. A minimally invasive treatment that clears vessels from encasing tumours is needed so more patients may undergo curative surgery. We hypothesise that effective ablation of perivascular tumours is possible through endovascular transcatheter photodynamic ablation (PDA).
Methods
Utilising in silico Monte Carlo calculations, the known needle-based photodynamic dose responses from previous Phase I/II studies were converted to endovascular transcatheter-based energy delivery. Subsequently, an in vivo dose escalation study in the porcine pancreas (n = 7) was performed utilising a prototype ablation catheter developed as part of this study.
Results
The simulations determined the recommended phase 1 PDA dose ranges to produce a 4, 8, or 12 mm margin of perivascular necrosis. In the porcine pancreas model, increasing doses produced increasingly large perivascular necrotic margins (0-15mm) while the vessel maintained its integrity for up to 7 days post-ablation, as determined by CT imaging and histopathology.
Conclusions
These proof-of-concept results demonstrate endovascular transcatheter PDA can produce adequate perivascular necrosis in a large animal model while preserving vessel integrity, justifying further investigation in Phase I/II clinical studies.
Revolutionizing Agriculture: Synergistic Antifungal Activity of Medicinal Plant Extracts against soil-borne phytopathogenic fungi
Authors: Malik Mansoor Ahmad , Ahmad Nusrat , Bhat Mohd Yaqub , Wani Abdual Hamid
Published: December 2024

A study was conducted to assess the effectiveness of various natural plant extracts on soil fungi, particularly targeting phytopathogenic and mycotoxigenic species Alternaria alternata, Fusarium oxysporum, Rhizoctonia solani, Cladosporium cladosporioides, Penicillium citrinum, Curvularia lunata, Fusarium metavorans, Fusarium solani and Aspergillus aflatoxiformans, were used in the present study. In vitro studies were carried out to evaluate the antifungal activity of three plant extracts performed both in aqueous and methanolic solutions. The findings indicated that the plant extracts exhibited robust antifungal activity, resulting in significant inhibition of mycelial growth across all tested fungi compared to the control. The extracts from Phytolacca acinosa and Atropa acuminata demonstrated the highest effectiveness in inhibiting the mycelial growth of the tested fungi, whereas Salix albaexhibited comparatively lower efficacy. The findings of this study validate the potential of plant extracts as natural fungicides for controlling pathogenic fungi, there by reducing dependence on synthetic fungicides. However, the extracts from Phytolacca acinosa and Atropa acuminata, identified as the most efficient, hold promise as potential agents for controlling these pathogenic fungi.
Transcriptomic Analysis of Differentially Expressed Lipid Metabolism-Related Genes and Immune Infiltration Characteristics in Psoriasis Patients
Authors: Yue Rui , Yang Peng , Xie Jie , Long Xinxin , Xie Aidi , Chen Yuxiang , Chen Xiaoli , Huang Yundi , Qiu Lifang , Peng Xuebiao
Published: December 2024

Psoriasis, a chronic and recurring disease, has a strong link to lipid metabolism. This study aims to identify differentially expressed genes (DEGs) and their functional pathways associated with psoriasis to uncover new therapeutic targets. We leveraged GEO datasets for DEGs analysis in psoriasis. GSEA, GSVA, WGCNA, & ssGSEA probed lipid metabolism genes' roles in psoriasis processes & immune changes. An RBP-mRNA network illuminated post-transcriptional regulatory mechanisms. Our findings revealed 3,839 DEGs, with 1,775 upregulated and 2,064 downregulated genes in psoriatic samples compared to controls. GSEA highlighted significant enrichment of immune-related pathways such as the cytosolic DNA sensing pathway and NOD-like receptor signaling pathway. WGCNA identified a black module strongly positive correlated with lipid metabolism containing 151 genes (r = 0.9216, p < 0.05). Enrichment analysis pointed to fatty acid metabolism and peroxisome pathways as critical in disease pathogenesis. Hub genes like AACS, HSD11B1 and GATA6 demonstrated high diagnostic potential with area under the ROC curve values exceeding 0.85. Immune infiltration analysis revealed significant differences in 27 types of immune cells between psoriasis and healthy control groups. Those findings provided a comprehensive molecular landscape of psoriasis, identifying potential new targets for therapeutic intervention and enhancing our understanding of the disease's underlying mechanisms.
Ultrasound Characteristics in Predicting Molecular Subtypes of Breast Cancer: A Retrospective Analysis
Authors: Zeinalkhani Fahimeh , Abbasi Mobina , Sadighi Nahid , Hakim Peyman Kamali , katouli Fatemeh shakki , Rahmani Shahriar , Tahamtan Mohammadreza
Published: December 2024

Objectives: Breast cancer, which is highly prevalent worldwide, presents with a range of molecular subtypes: luminal A (LA), luminal B (LB), triple-negative (TN), and HER2 positive (HER2+), each with unique prognostic and treatment implications. The utility of breast ultrasound in predicting these subtypes remains underexplored.
Methods: This retrospective study analyzed data from 140 women with primary invasive breast cancer treated at the Cancer Institute from April 2022 to March 2023. Standard ultrasound imaging and comprehensive clinical-pathological data, including molecular subtypes identified via immunohistochemistry, were used. Statistical analysis was performed with SPSS (version 22), focusing on correlations between ultrasound features and molecular subtypes.
Results: The average age of participants was 49.75 years, with tumor sizes averaging 27.1 mm. LA was the most common subtype (48%), followed by LB (25%), TN (18%), and HER2+ (7%). Significant correlations were found between ultrasound features and molecular subtypes, particularly the presence of calcification and tumor shape. The TN type showed the highest calcification rate (30.7%), followed by the LA subtype at 29.4%. The irregular shapes across all subtypes were a common morphological characteristic, while the variation in the frequency of round and oval shapes highlights potential subtype-specific differences.
Conclusions: Ultrasound features correlate with specific molecular subtypes of breast cancer, suggesting potential diagnostic value in subtype differentiation. However, limitations such as the single-center scope and small sample size may affect the generalizability of the findings. Further research is needed to validate these preliminary results and potentially expand the diagnostic capabilities of ultrasound in breast cancer subtyping.
Effects of short-term melatonin supplementation on sleep quality in college students with high frequency of screen-based sedentary behaviour: a two-stage study
Authors: You Chuanqi , Cui Yupeng , Yang Shaofeng , Ren Zhe
Published: December 2024

Objective
This study aims to further clarify the association between Screen-Based Sedentary Behavior (SSB) and sleep quality, and to explore the effects of short-term melatonin supplementation on the sleep quality of college students with high-frequency screen-based sedentary behavior.
Methods
The study is divided into two phases. Phase one is a cross-sectional study involving 104 college students, where we assessed the relationship between SSB and sleep quality in college students, as well as the differences in sleep quality among students with varying frequencies of SSB. In phase two, 40 participants were recruited from those screened in phase one to participate in a melatonin intervention experiment, utilizing a 2x2 factorial experimental design: melatonin with high-frequency SSB (HM, n = 10), placebo with high-frequency SSB (HP, n = 10), melatonin with low-frequency SSB (LM, n = 10), and placebo with low-frequency SSB (LP, n = 10). Measurement indicators included PSQI scores, sleep duration, bedtime, wake-up time, sleep latency, and sleep efficiency to evaluate improvements in sleep quality after melatonin/placebo interventions.
Results
Phase one results indicated a significant correlation between SSB and PSQI scores (r = 0.845, P < 0.01), sleep duration (r=-0.66, P < 0.01), bedtime (r = 0.76, P < 0.01), and sleep efficiency (r = 0.734, P < 0.01). There was a significant difference in sleep quality between the low-frequency and high-frequency groups (P < 0.001). In phase two, after melatonin/placebo intervention, the HM group showed significant improvements in PSQI scores, sleep duration, bedtime, sleep latency, and sleep efficiency (P < 0.01). Additionally, there were no significant differences in sleep quality and related variables among the HM, LM, and LP groups post-intervention.
Conclusions
There is a significant correlation between SSB and sleep quality, with higher SSB associated with poorer sleep quality. The sleep quality of college students with high-frequency SSB can be significantly improved through short-term melatonin supplementation, indicating a potential beneficial intervention effect of melatonin in this population.
Surgical outcomes of cervical spinal cord tumor in elderly patients assessed by the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire
Authors: Nagoshi Narihito , Ito Shuhei , Okubo Toshiki , Ozaki Masahiro , Suzuki Satoshi , Takeda Kazuki , Iga Takahito , Matsumoto Morio , Nakamura Masaya , Watanabe Kota
Published: December 2024

Study Design. Single-institution retrospective study
Objectives. To assess postoperative functional and quality of life (QOL) outcomes in elderly patients who underwent cervical spinal cord tumor surgery using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ).
Setting.
Single university hospital
Methods. This retrospective study included 97 patients who underwent surgery for cervical spinal cord tumors between 2000 and 2016. Patients were divided into two groups: a younger group (patients <65 years old) and an elderly group (patients ≥65 years old). Surgical outcomes were evaluated using JOA scores and JOACMEQ, with statistical comparisons between age (younger vs. elderly) and tumor types (intramedullary vs. extramedullary).
Results. Preoperative JOA scores were significantly lower in the elderly group compared to the younger group. Postoperative recovery rates were similar between the two groups. Extramedullary tumor resections in the elderly showed notable functional improvements. Conversely, elderly patients with intramedullary tumors exhibited poorer outcomes in lower extremity function and QOL, as measured by the JOACMEQ.
Conclusion. Surgical intervention for cervical spinal cord tumors in elderly patients can yield functional and QOL outcomes similar to those in younger patients, especially for extramedullary tumors. However, intramedullary tumor resections in the elderly may result in less favorable outcomes, particularly in lower limb function and QOL. These findings underscore the importance of thorough preoperative counseling for elderly patients, highlighting potential risks and benefits based on tumor type.
Anti-cancer effect of Mesenchymal Stem
Authors: Khalil Charbel , Gemayel Jack , Salameh Rawad , Haddad Lara , Ghanem Hady , Moutran Dina , Akouch Khalil , Hachem Georges , Rustom Majed , Hanna Colette , Ibrahim Ahmad , Ghadieh Hilda , Harb Frederic
Published: December 2024

Despite the fact that MSCs are clearly associated to tumor development, the absence of methods for precisely identifying the various MSC populations and the paradoxical association between MSC and tumor has hampered the development of MSC-based oncological therapies. In this study, we try to investigate the effects of human umbilical cord derived (UC-MSCs) and their secretome, alone or compared to 5-FU, on the proliferation of CRC cell lines, their migration ability, and their expression of tumor markers. Chemotherapy combinations including 5-fluorouracil (5-FU) have been the gold standard in the treatment of CRC, but their use is hindered by the development of side effects or chemo-resistance by patients. On the other hand, umbilical cord-derived mesenchymal stem cells (UC-MSCs), bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AT-MSCs) and their immunomodulatory cytokines and chemokines, known as the MSC secretome, are showing favorable effects on immune and inflammatory diseases in clinical trials. Due to their tropism to inflammatory signals, mesenchymal stem cells have been used for cell therapy or as a vehicle to deliver therapeutics to tumors. Measurements of colorectal cancer tumor marker proteins were computed by ELISA. Proliferative, apoptosis and anti-inflammatory effects of the MSCs were measured by Flow cytometry (FCM). MMPs expression was measured by RT-PCR.
Which technique is preferable for grade 2-3 hemorrhoidal disease: Laser vs. rubber band ligation?
Authors: EMRAL Ahmet Cihangir , GULEN Merter , EGE Bahadır
Published: December 2024

BACKGROUND
The aim of this study is to compare the short and long-term results (postoperative pain, complications, return to daily life, recurrence) between patients who underwent hemorrhoids laser procedure (HeLP) and rubber band ligation (RBL) due to grade 2–3 hemorrhoidal disease.
METHODS
The results of patients who underwent HeLP and RBL between June 2020 and June 2023 for grade 2–3 hemorrhoidal disease were evaluated retrospectively. The patient information was examined in terms of operation time, postoperative 1st, 7th and 14th day visual analog scale (VAS) values, the amount of analgesic used in the first 7 postoperative days, return to normal life (days), recurrence within 1 year and other complications (postoperative bleeding, thrombosis, urinary retention, infection/abscess, anal stenosis, deterioration in continence).
RESULTS
A total of 260 patients were included in the study, 166 of whom underwent RBL and 94 HeLP. Operation time, hospital stay (hours), VAS values, postoperative 7-day analgesic use (mg), worsening of incontinence, time to return to normal life (days), complications and recurrence within 1 year evaluated. HeLP has statistically significant lower postoperative 1st day pain and less analgesic use (mg) than RBL (p < 0.001).
CONCLUSIONS
The reduced pain and fewer analgesic use provided by HeLP, especially on the first postoperative day, improves patients' satisfaction.
Quantifying Climate Change Risk through Natural Hazard Losses to Inform Adaptation Action
Authors: Mongold Emily , Baker Jack W.
Published: December 2024

Climate change is expected to increase the frequency and severity of many natural hazards. In particular, coastal communities are often exposed to multiple hazards, exacerbated by climate change. We present a methodology to quantify the increase in multi-hazard risk due to climate change. The methodology includes probabilistic description of independent hazard pathways, defined as sets of individual and cascading hazards that are statistically independent, run for multiple levels of climate change impact. We also quantify the risk reduction from adaptation actions. The approach integrates probabilistic hazard analysis and loss assessment. With this approach, we identify the hazards contributing most to risk under multiple amounts of climate change. This methodology is applied to a case study of residential housing in Alameda, California, USA, considering how sea level rise impacts multiple hazards: earthquakes, coastal flooding, and tsunamis. For the case study location, we identify the highest risks shift from earthquakes to coastal flooding as sea levels rise. We assess how different adaptation actions would reduce the risk today and under sea level rise, highlighting the need to consider frequent and infrequent losses.
Australian and New Zealand medical students’ confidence and preparedness to prescribe
Authors: Mokrzecki Sophie , Perks Stephen , Pain Tilley , Gupta Tarun Sen , Mallett Andrew
Published: December 2024

Background
Writing a medication prescription is an expected competency junior doctors internationally feel underprepared to complete. Providing clarity in medical prescribing education standards and assessment criteria may address the lack of preparedness.
The primary aim of this study is to understand Australian and New Zealand (NZ) final-year medical students’ confidence and preparedness to write a discharge or outpatient prescription. Secondarily, identify by whom, when, and using what modalities education on prescription writing should be provided.
Methods
This quantitative analytical cross-sectional survey was developed through REDCap®. Ethical approval allowed email survey distribution to participants from June to December 2022. Data was analysed using IBM SPSS v29. Likert-scale responses were cross tabulated against participant confidence and preparedness to handwrite and electronically write discharge or outpatient prescriptions. Mixed model logistic regression analyses determined the preferred education modalities, educator, and time during medical degree to receive prescription writing education.
Results
Final-year medical students from Australia (n=123) and NZ (n=51) completed the survey. Participants felt their university degree didn’t increase their confidence or preparedness to electronically or hand-write prescriptions. Learning on placement was significantly most desirable in comparison to other options. Majority of participants selected pharmacists as the educator and their final year as an ideal time during their medical degree to receive education on prescription writing.
Discussion
The absence of mandated education and assessment on the skill to prescribe was evident. The results showed aself-acknowledgement of under-preparedness and confidence to write medication prescriptions. This suggests a need for further education and specific assessment standards on the skill of prescription writing.
Conclusion
Pharmacist-led mixed-methods education model during the final year of medical education is suggested to address gaps in education and assessment on prescription writing. Providing further education on the skill of prescription writing before graduation may reduce prescribing errors made as junior doctors.
Rapamycin Rescues APC-Mutated Colon Organoid Differentiation
Authors: Ben-Yosef Dalit , Habib Aline , Mamistvalov Rose
Published: December 2024

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by germline mutations in the adenomatous polyposis coli (APC) gene. This leads to numerous colorectal adenomas and a high risk of colorectal cancer (CRC). Our stem cell-derived colon organoid model revealed that a heterozygous APC mutation is sufficient to induce colorectal cancer formation. We found a link between APC mutation type, organoid maturation and FAP severity. Here we show that severe germline mutations in hESCs employ diverse mechanisms of carcinogenesis. FAP1-hESCs expressing a truncated 332-amino acid protein exhibited a hyperactivated mTOR pathway, including PTEN inactivation and increased S6K1 and eIF4E activation. This affected oncogenic c-Myc expression and contributed to apoptosis resistance. Rapamycin treatment restored differentiation potential in FAP1 organoids but not FAP2 organoids, which expressed a larger truncated protein without mTOR pathway activation. Our in-vitro colon organoids system findings were validated in human patients. Notably, a colon from a FAP1 patient exhibited high expression of mTOR pathway proteins. These findings highlight the potential of rapamycin for personalized therapy in FAP patients with distinct mTOR-mediated APC mutations. Our colon organoid model is valuable for studying CRC and developing new diagnostic, preventive, and therapeutic approaches to prevent or delay tumorigenesis in FAP patients.
Analysis and Validation of the Glasgow Prognostic Score (GPS) for Predicting 14-, 21-, and 30-Day Mortality in End-Stage Cancer Patients
Authors: Huang Jhen-Ling , Yang Wan-Ling
Published: December 2024

Background: The Glasgow Prognostic Score (GPS) is commonly used to evaluate cancer patient prognosis. Early initiation of palliative care for end-stage cancer patients is crucial in providing comfort and preparing both patients and their families for a peaceful death. This study aimed to assess the value of GPS in predicting short-term mortality in end-stage cancer patients.
Methods: A retrospective analysis of in-hospital cancer deaths at a medical center in Taiwan over a five-year period was conducted. The discriminative ability, accuracy, sensitivity, specificity, and positive and negative predictive values of GPS were evaluated using the area under the receiver operating characteristic curve (AUC) for predicting 30-, 21-, and 14-day mortality.
Results: Among the 5,315 in-hospital cancer deaths between 2009 and 2013, 78% of patients died within 30 days of admission (mean hospital stay = 12 days). The GPS scoring model’s predictive ability for short-term mortality was suboptimal for this cancer population (AUC = 0.548, 95% CI: 0.526–0.571). Although sensitivity was high (79.2%), specificity was low (30.3%), and overall accuracy was 68.0%.
Conclusion: The GPS scoring model has high sensitivity and may serve as a reference for initiating palliative care in end-stage cancer patients. However, due to its low specificity, caution should be exercised in applying GPS scores for end-of-life care planning and patient communication, as it does not accurately predict patient death.
High Schistosoma mansoni infection intensity is associated with distinct gut microbiome and low levels of systemic cytokines in children along the Albert-Nile, Northern Uganda
Authors: Mulindwa Julius , Lujumba Ibra , Musiime Caroline , Namulondo Joyce , Kimuda Magambo Phillip , Nyangiri Oscar , Cuu Gloria , Mwubaha Caroline , Tukwasibwe Stephen , Ssemaganda Aloysious , Ssewanyana Isaac , Nerima Barbara , Baingana Rhona , Noyes Harry , MacLeod Annette , Matovu Enock
Published: December 2024

Background
Schistosomiasis is a chronic neglected disease that affects millions of people in sub Saharan Africa, with a range of impacts on both host immune responses and the gut microbiome. The gut microbiota plays a fundamental in role in the host’s nutrition, metabolism, protection against pathogens, and modulation of host immunity. There is a need to understand the role of the gut microbiome in pathophysiology of Schistosoma mansoni infection and how this influences the host’s immune response.
Methodology:
A cross sectional study was carried out on 140 faecal samples collected from school children aged 10-15years residing in the schistosomiasis endemic hot spots of the Albert-Nile, Pakwach district, Northern Uganda. The samples were categorised by S. mansoni infection intensity based on the Kato Katz test. Faecal DNA was isolated and microbiome composition was determined by 16S rRNA V3-V4 sequencing. Plasma Th1/Th2 profiling of 13 cytokines was carried out on the Luminex platform and compared with respect to S. mansoni infection intensities.
Results
The genera Phascolarctobaterium and Prevotella_7 were significantly enriched (padj < 0.05, LDA > 3.0) in the high S. mansoni infection intensity group whereas, Ruminobacter and Alloprevotella were enriched in the Low infection intensity group. We observed significantly lower systemic Th1/Th2 cytokine levels between the high intensity infection and the control samples (padj < 0.05). Linear regression analysis using all cytokines as covariates showed that the genus Alloprevotella, Streptococcus, Gastranaerophilales and Ruminobacter were associated with systemic IL6 response.
Conclusion
There are alterations in the gut microbiome of S. mansoni infected children with distinct genera that discriminate the high and low infection intensity that could be potentially used as biomarkers. There is an association between the gut microbiome and systemic cytokine response whose mechanism in chronic disease pathophysiology can be further investigated.
Development and Validation of a Machine-Learning Model for Predicting Prognosis in Critically Ill Patients Undergoing Major Surgery
Authors: Zhang Xian , Wang Tao , Chen Zhe , Zhang Shuliu , Yuan Jihong , Qin YingYi , Cui Yunliang
Published: December 2024

Background
Major surgery can result in elevated mortality rates, poorer prognoses, and extended hospital stays. This study sought to develop and validate an effective machine-learning model capable of accurately forecasting outcomes in critically ill patients who have undergone major surgery.
Methods
Using the publicly accessible Medical Information Mart for Intensive Care (MIMIC)-IV database, we developed and validated multiple machine-learning models to predict postoperative outcomes in critically ill patients who had at least an overnight ICU stay after major surgery. Seven predictive models were tested to forecast prognosis, with the highest-performing model selected based on its accuracy and the area under the receiver operating characteristic curve (AUC). An advanced model, eXtremely Gradient Boosting (XGBoost), was created using all variables, followed by a streamlined model built from 10 features chosen for their importance and clinical applicability. The performance of both models was assessed using Decision Curve Analysis (DCA), while survival analyses distinguished high- and low-risk groups within the internal validation sets.
Results
A cohort of 2,335 critically ill patients who had undergone major surgery were included in the MIMIC-IV cohorts. The full XGBoost model achieved an accuracy of 80.6% and an AUC of 0.828, indicating high predictive power. A more practical selection model with 10 features demonstrated a slightly lower AUC of 0.824 (95% CI: 0.762–0.886) but offered advantages in clinical usability. The ten key features were identified based on their SHapley Additive exPlanations (SHAP) values, which included the Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS)-II, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, ARDS and sepsis complications, blood urea nitrogen (BUN) levels, estimated glomerular filtration rate (eGFR), respiratory rate, and marital status. Additionally, survival curves showed a clear distinction between high- and low-risk groups based on predictions from both the full and selection XGBoost models.
Conclusions
This study developed two XGBoost model variants that outperform other ICU predictive methods for forecasting the prognosis of patients undergoing major surgery. These models have the potential to assist healthcare providers in making more informed decisions, thereby improving clinical outcomes in the ICU setting.
Effects of Mirror Therapy Preceding Augmented Reality in Stroke Rehabilitation: A Randomized Controlled Trial
Authors: Lin Chia-Jung , Lin Keh-chung , Lau Hiu-Ying , Hsieh Yu-wei , Li Yi-chun , Chen Wen-Shiang , Chen Chia-Ling , Chang Ya-Ju , Lee Ya-Yun , Yao Grace , Hrong Yi-shiung , Pan Hsiao-Chieh , Wu Yi-Hsuan , Hsu Wan-Ling , Kuo Chih-chieh , Tsai Han-ting , Lin Chih-yu , Chang Pin-chen
Published: December 2024

Background
Mirror therapy (MT) and augmented reality (AR) are gaining popularity in stroke rehabilitation. MT uses mirror visual feedback to promote bilateral brain coupling and increase primary motor cortex excitability. AR offers an interactive context of practice for promoting motor and cognitive recovery. MT and AR may complement each other for hybrid interventions in stroke rehabilitation. This study investigated the differential benefits of AR compared with conventional therapy (CT) and evaluated the efficacy of an MT-primed intervention versus AR alone for individuals with stroke.
Method
The study randomly assigned 44 stroke survivors to the MT-primed AR group (MT + AR), the AR group (AR), or the CT group. Each treatment session was 90 minutes, 3 times a week, for 6 weeks. All assessments were administered before, immediately after treatment, and at 3 months. Primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Berg Balance Scale (BBS). Secondary outcome measures were the revised Nottingham Sensory Assessment (rNSA), Chedoke Arm and Hand Activity Inventory (CAHAI), Motor Activity Log (MAL), and Stroke Impact Scale Version 3.0 (SIS). Adverse events were monitored before and after each session.
Results
After 6 weeks of treatment, the three groups demonstrated significant improvements in the FMA-UE, BBS, CAHAI, MAL, and SIS. In the between-group comparisons, MT + AR demonstrated a significant advantage in the FMA-UE (p = 0.03). On the other hand, AR showed greater improvements in the BBS (p < 0.01). Regarding secondary outcome measures, MT + AR exhibited significant changes in rNSA, with a notable advantage in tactile sensation in between-group comparisons (p < 0.01). The MT + AR and the AR groups both showed significant improvement in proprioception of rNSA and SIS compared with the CT group. Most of these changes were retained through the 3-month follow-up. No adverse effects were observed.
Conclusion
MT + AR and AR both effectively enhanced sensorimotor functions, balance, task performance, and life quality in patients with stroke with moderate to severe motor impairments. Each therapy demonstrated its strength: MT + AR was more beneficial for improving upper limb motor function and sensory function, whereas AR excelled in balance and functional mobility. Clinical therapists should consider stroke survivors’ goals and select appropriate intervention protocols.
Trial registration
NCT 05993091
Fallowed agricultural lands dominate anthropogenic dust sources in California.
Authors: Adebiyi Adeyemi , Kibria Md. Minhazul , Abatzoglou John , Ginoux Paul , Pandey Satyendra , Heaney Alexandra , Chen Shu-Hua , Akinsanola Akintomide
Published: December 2024

Air pollution remains a major problem in many parts of California, significantly impacting public health and regional climate. However, the contribution of anthropogenic dust particles from agricultural sources, among the major pollutants, in California's semi-arid Central Valley region remains largely unclear. Here, we used the Cropland Data Layer from the US Department of Agriculture to identify crop types and land cover and leveraged satellite-derived estimates of major anthropogenic dust events between 2008 and 2022 over California. We identified fallowed land – an unplanted agricultural land parcel – as a key anthropogenic dust source in California. Specifically, we find that the Central Valley region accounts for about 77% of total fallowed land areas in California, where they are associated with about 88% of major anthropogenic dust events. We also find that regions with higher coverage of fallowed lands are expanding, increasing anthropogenic dust activities over the period considered. Additionally, these anthropogenic dust activities are sensitive to the dryness levels over the fallowed lands, with potential cumulative effects on downstream dust burden during prolonged multi-year drought conditions. Overall, our results have important implications for public health, including possible increased risk for Valley fever, a fungal respiratory infection caused by inhalation of soil-dwelling infectious spores, and on regional climate, such as increases in extreme precipitation and snowmelt over the Central Valley and the Sierra Nevada.
Endovascular treatment beyond 24 hours for large vessel occlusion strokes selected by CT perfusion
Authors: Wu Changzhu , Wang Xianwei , Ni Hong , Wang Feng , Hong Weijun , Jiang Yiqing , Chen Liujing , Wang En
Published: December 2024

Background
The role that endovascular treatment (EVT) may play in stroke patients with large vessel occlusion (LVO) who are treated beyond 24 hours after onset is unclear. In this study, we aimed to examine the efficacy and safety of EVT beyond 24 hours based on uniform CT perfusion criteria in appropriately selected patients.
Methods
A retrospective review was performed at a single stroke center between January 2020 and August 2023. We chose patients who received EVT beyond 24 hours via CT perfusion. A matched group of patients who received EVT within the 6–24 hour time window was chosen as a control. Functional independence (modified Rankin scale score ≤ 2) at 90 days was used as the primary outcome, and symptomatic intracranial hemorrhage (sICH)and mortality were considered safety outcomes.
Results
We selected 400 patients treated with EVT within the 6–24 hour time window and 82 patients treated beyond 24 hours. A 2:1 matched group was used for comparison. No significant differences in functional independence (58.5% vs. 61.6%, P = 0.645), safety outcomes of sICH (7.3% vs. 9.8%, P = 0.527), or mortality (2.4% vs. 3.0%, P = 0.786) at 90 days were demonstrated. Patients who underwent EVT beyond 24 hours had a greater incidence of large-artery atherosclerosis (LAA) (89.0% vs. 75.6%; P = 0.044) and a course of neurological deterioration before EVT (78.0% vs. 43.7%; P < 0.001). According to multivariate analysis, the preoperative NIHSS score (OR = 0.770, P = 0.001), sex (OR = 4.569, P = 0.007), and pro-operative ND (OR = 27.192, P = 0.006) were associated with good outcomes.
Conclusions
Compared with endovascular treatment performed within the 6–24 hours, EVT beyond 24 hours appears to be feasible and safe for acute LVO stroke patients who meet the DEFUSE-3 imaging criteria based on CT perfusion. Patients with neurological deterioration during the course of the disease may be a suitable screening population for super late window EVT.