bluuebunny/crossref_metadata_2025 huggingface dataset:
Laccase-Catalyzed Cycloaddition (LaCCA) Reaction: An Efficient Green Approach for Synthesizing Mono- and Bis-(1,4-Disubstituted-1,2,3-Triazoles) via Click Chemistry—In Silico Molecular Docking and Druglikeness Assessment
Authors: Gupta Swati , Narula Anudeep Kumar
Published: January 2025

Background:

Mono- and bis-(1,4-disubstituted-1,2,3-triazoles) were synthesized via a
laccase-catalyzed reaction using Trametes versicolor. This methodology offers a convenient and
efficient approach to triazole synthesis under mild conditions, achieving modest to good yields.
Additionally, molecular docking studies were performed using PDB IDs 2W9S (antibacterial) and
3KHM (antifungal) to evaluate biological activities. The results of drug-likeness analysis further
corroborated the findings from experimental biological evaluations.

Methods:

This study focuses on developing an eco-friendly method for synthesizing novel 1,2,3-
triazole derivatives using a green catalyst. A co-solvent buffer and organic solvent facilitate the
reaction, which performs well with various substrates, including substituted benzenes (-ortho, -meta
& para-mono & bis-(2-propynyloxy), sodium azide, and aryl halides. Laccase enzymes from
Trametes versicolor are used, leveraging naturally occurring copper metals instead of external transition
metals, bound through histidine, methionine, and cysteine linkages. This method represents
a sustainable approach to organic transformations.

Result:

New scaffolds of mono- and bis-(1,4-disubstituted-1,2,3-triazoles) were synthesized using
eco-friendly green buffer solvents and laccase catalysis with aryl halides, sodium azide, and acetylene
derivatives. Molecular docking studies revealed that the binding affinities of the synthesized
compounds (1-14) show promising interactions with antibacterial and antifungal proteins. All others
except for compounds 6, 7, 8, 12, and 13, meet Lipinski’s criteria, making them potential therapeutic
candidates.

Conclusion:

In conclusion, this methodology is valuable for developing antibacterial and antifungal
agents in medicinal chemistry. Additionally, microwave-assisted synthesis of (2-propenyloxy)benzene
derivatives significantly reduced reaction times from hours to minutes. The approach is environmentally
friendly and practical, particularly for handling flammable organic azides and hazardous
solvents, making it both efficient and safer.
HA-SCINet based Carbon Emission Prediction of the Typical Park
Authors: Zeli Wang , Zeyu Liu , Xupeng Song , Guangtao Wei , Mingchun Li , Hongjun Huang , Weiqi Shao , Yuancheng Li
Published: January 2025

Background:

With the rapid economic growth and the accelerated process of industrialization,
the production activities of enterprises within parks have significantly increased, leading
to a continuous rise in carbon emissions. Under the context of the "dual carbon" goals, studying
the prediction of carbon emissions in typical parks holds significant practical importance. It is not
only a key measure to address climate change but also an important pathway to achieve sustainable
development.

Objective:

In order to predict the carbon emissions of the typical park more accurately, we propose
a carbon emissions prediction model HA-SCINet.

Methods:

The model uses a recursive downsampling-convolution-interaction architecture. In each
layer, the long-term dependence in time series data is extracted by HyperAttention. Then through
the L-layer SCI-Block of the binary tree structure, the down-sampling interactive learning extracts
both short-term and long-term dependencies. These extracted features are merged and reorganized,
and added to the original time series to generate a new sequence with enhanced predictability.
Finally, employ a fully connected network for forecasting the enhanced sequence. The carbon
emission data of the typical park serve as input, leading to higher accuracy prediction results
through the Stacked K-layer stacked HA-SCINet.

Results:

The mean square error (MSE) and mean absolute error (MAE) of HA-SCINet prediction
model are 0.0819 and 0.204 respectively, outperforming the mainstream Dlinear and Nlinear models

Conclusion:

The experimental results show that the devised model outperforms in predicting carbon
emissions, and is better suited for forecasting carbon emissions within the context of the typical
park.
Short-term Load Forecasting Method Based on VNCMD-TiDE Model
Authors: Sun Bohao , Pei Yuting , Wang Zesen , Han Junjie
Published: January 2025

Background:

Extreme weather conditions exert a considerable influence on power
load, leading to increasingly erratic fluctuations. Consequently, the dependable and precise forecasting
of power load assumes paramount importance in power system planning.

Objective:

Given the inadequacy of traditional forecasting approaches in handling long-term series
load forecasting, this paper introduces a short-term power load forecasting model rooted in
VNCMD-TiDE, aiming to enhance forecasting precision.

Method:

Initially, the XGBoost algorithm is employed to perform nonlinear coupling analysis
between load and meteorological data, identifying crucial features. Following this, the VNCMD
method is utilized to handle the nonlinear and non-stationary load data, decomposing it into multiple
components with distinct frequencies. Building upon this decomposition, a TiDE-Bayesian
model is constructed, wherein the decomposed components serve as inputs for prediction. Simultaneously,
Bayesian optimization is leveraged to fine-tune hyperparameters. Ultimately, the prediction
outcomes of each component are amalgamated to derive the final prediction.

Results:

The proposed model's performance is assessed through comparison with traditional machine
learning models, such as LSTM. Achieving a noteworthy reduction in Root Mean Square
Error (RMSE) by 4.14 underscores its exceptional predictive prowess.

Conclusion:

Through the analysis of actual power load data in a specific location, the model
proposed in this article demonstrates superior prediction accuracy, particularly evident during extreme
weather conditions like snow and rain.
Optimizing Cloud Traffic Offloading and Cloudlet Resource Usage in Cloud-Integrated WOBAN (CIW)
Authors: Verma Mausmi , Bhatt Uma Rathore , Upadhyay Raksha , Bhat Vijay
Published: January 2025

Background:

Integration of cloud components in a wireless mesh network of Wireless-
Optical Broadband Access Network (WOBAN) contributes to enhancing network performance.

Aim:

This study aims to deploy the minimum cloudlets at the optimum location and to offload
excess traffic from overloaded cloudlets to underloaded ones.

Objective:

The objective of this study is to optimize cloudlet positioning and traffic offloading for
cost-effective deployment, better resource utilization, reduced blocking probability, and lower
delays.

Method:

The proposed methodology introduces a Cluster-Based Heuristic Approach (CBHA) for
efficient cloudlet placement along with a traffic offloading mechanism using a Customized Donkey-
Smuggler Optimization (CDSO) to enhance the overall network performance.

Result:

Simulations show the effectiveness of the proposed approach for resource utilization,
blocking probability, delay, and cost.

Conclusion:

The problem in position optimization of the cloudlet, along with traffic offloading, is
solved using the proposed approaches to get better network performance in a cost-efficient manner.
Recent Developments of Solar Charge Controllers Technologies: A Bibliometric Study
Authors: Azhar A.D. , Arsad A.Z. , Yew W.H. , Ghazali A. , Chau C.F. , Zuhdi A.W.M.
Published: January 2025

A solar photovoltaic system is a renewable energy that depends on solar irradiance
and ambient temperature. A solar charge controller is required to ensure the energy received by
the photovoltaic cell or module is maximized at the output. This study presents the first bibliometric
analysis based on a thorough evaluation of the most frequently cited articles on the solar
charge controller to forecast future trends and applications. This paper performs a statistical
analysis using the Scopus database and extracts the 100 most cited papers. It has been illustrated
that the solar charge controller literature expanded swiftly from 2012 to 2023, with 2019 receiving
the most publications and papers published in 2018 receiving more citations compared to
works published in other years. In recent years, battery storage, electric vehicles, energy storage,
controllers, photovoltaic systems, and power management systems have garnered great interest.
The solar charge controller's functional evaluation and determination of the optimal renewable
energy system might boost its potential. Our analysis of highly cited articles on solar charge
controllers emphasizes a selection of features, including control methods and systems, issues,
challenges to establishing current constraints, research gaps, and the need to find solutions and
resolve problems. Every aspect of the features of this overview is anticipated to contribute to an
upsurge through the invention of advanced solar charge controllers and control methods for future
photovoltaic systems.
Plant-based Therapeutics for Aspergillus Co-infections in COVID-19
Patients Illuminating Phytochemical Mechanisms
Authors: Singh Harjeet , Pandya Shivani R. , Yadav Alpa , Dhanda Parmdeep Singh , Kaushik Prashant , Jain Mukul
Published: January 2025

The emergence of COVID-19 has highlightedthe issue of secondary fungal infections,
such as COVID-19-Associated invasive Pulmonary Aspergillosis (CAPA), in critically ill patients.
Continuous use of therapies employing steroids and immune-modulating agents has increased the
risk of co-infections resulting from fungi, further weakening the respiratory systems of patients and
leading to complex situations such as multi-organ failure and elevated mortality. The increasing occurrence
of antifungal resistance in Aspergillus strains has made the management of these infections
challenging, highlighting the need for novel and effective antifungal agents. Plants and their bioactive
compounds offer promising alternatives to conventional antifungal medications. Phytochemicals
such as 1,8-cineole from Eucalyptus, thymol from commercial extracts, and cinnamaldehyde from
cinnamon have demonstrated significant antifungal activities by targeting fungal cell walls, membranes,
and gene expression. Additionally, compounds like eugenol from cloves and citral from
lemongrass exhibit potent antimicrobial effects by disrupting cellular integrity. However, challenges
such as variability in phytochemical content, limited clinical data, and potential drug interactions
must be addressed. This review explores the potential of plant-based medicines for treating aspergillosis,
emphasizing the need for further research to validate their effectiveness, safety, and optimal
dosages through clinical studies.
Deposition of Abnormal Proteins in the Brain
Authors: Wang Gaiqing , Chen Haiyun , Yang Juan , Wang Jing , Yan Bo , Chen Minglei
Published: January 2025

A common feature of neurodegenerative diseases is the abnormal
accumulation of misfolded proteins in the brain, such as amyloid beta (Aβ), tau, αsynuclein, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43),
which lead to selective neuronal degeneration and dysfunction. Dysfunction in the
removal of these misfolded proteins from the brain, which is thought to be a major
cause of neurodegenerative diseases and a major therapeutic target for their cure.
Response to Foreign Pathogens in the Brain
Authors: Wang Gaiqing , Chen Haiyun , Yang Juan , Wang Jing , Yan Bo , Chen Minglei
Published: January 2025

The brain's defense against foreign invaders involves a specialized immune
system called the neuroimmune system. It includes microglia, astrocytes, and other
immune cells. Microglia detect and respond to abnormalities, while astrocytes help
maintain the blood-brain barrier and participate in immune signaling. Together, these
cells protect the brain from pathogens and maintain its health. Understanding the
neuroimmune system is crucial for combating brain infections and inflammatory
disorders.
The Function of Neurovascular Unit in Clearance System
Authors: Wang Gaiqing , Chen Haiyun , Yang Juan , Wang Jing , Yan Bo , Chen Minglei
Published: January 2025

The neurovascular unit (NVU) encompasses multiple cellular elements such
as the BBB, astrocytes, microglia, and pericytes. Together, these components form a
system that aids in the removal of waste products, toxins, and surplus neurotransmitters
from the brain tissue. The NVU's functions include circulatory regulation, perivascular
drainage, and phagocytic degradation clearance systems. Its pivotal role lies in
preserving brain homeostasis and thwarting the buildup of detrimental substances that
might otherwise impede regular brain function.
The Role of Meningeal Lymphatic Systems
Authors: Wang Gaiqing , Chen Haiyun , Yang Juan , Wang Jing , Yan Bo , Chen Minglei
Published: January 2025

The meningeal lymphatic system is a newly identified network of lymphatic
vessels located within the meninges, the protective membranes enveloping the brain
and spinal cord. This system is essential for clearing waste products, supporting
immune responses, and ensuring the balance of brain functions.
The Regulatory Mechanism for Scavenging Pathways
Authors: Wang Gaiqing , Chen Haiyun , Yang Juan , Wang Jing , Yan Bo , Chen Minglei
Published: January 2025

Scavenging pathways are essential for cells to recycle and reuse cellular
components. These pathways are regulated by a complex network of mechanisms that
ensure efficient scavenging and recycling of cellular materials. The regulatory
mechanisms involved are intricate and interconnected, employing multiple levels of
control to facilitate the proper recycling and reuse of cellular components.
In our previous discussions, we outlined the upstream regulatory mechanisms and
intervention strategies for scavenger receptors following ICH [44].
A Study on the Interpretation of the Scripturesin Ganjae's Daehakgieui
Authors:   The Association of DaeDong-Hanmun, Gil Tae-eun
Published: January 2025

The purpose of this article is to examine the characteristics of Ganjae Jeonwoo interpretation of the scriptures through the contents of the commentary in Daehakgieui. Since the analysis of Daehakgieui. has been conducted in a consultative manner on almost fragmentary matters so far, it is necessary to review what perspective or intention was written with the overall perspective. In other words, it can be inferred that he would have analyzed the scriptures through the theory of Neo-Confucianism as a Neo-Confucianist and pursued Taoism as a preacher of Nakron, and these points were examined intensively. Ganjae's interpretation of the scriptures is introduced as the main idea of the scriptures and the theory of Neo-Confucianism, but if it goes against the main idea, not only the main theory but also the teacher of Neo-Confucianism takes an unyielding attitude and criticizes it. The reason for showing a strict academic attitude that excludes these opinions is the demonstration of efforts to pursue suspension and reject heresy, and it can be interpreted as the result of consciousness of symbolism as an evangelist. The spirit of overseeing Ganjae's thoughts can be expressed as ‘Simbonseong’, but if it encompasses his psychology, it is not unreasonable to call it the mindfulness, ‘Jonsungmyeonggi’ or ‘Jonsungyanggi’. These points inevitably lead to differences in the perception and response of reality with the characters at the time as the enemy of Ganjae's preference. Therefore, it can be evaluated that Ganjae's Gyeonghak thought is a Jujahak Gyeonghak or a Librarian- centered Gyeonghak that explores the original intention of the scriptures with Neo-Confucianism theory, and Ganjae's Gyeonghak can be evaluated as a Dohak Gyeonghak that pursues Dohak as an evangelist again.
Sendero dependencia en presencia de militares chilenos en catástrofes
Authors: Baeza-Freer Jaime , Escudero-Illanes María Cristina
Published: January 2025

Este trabajo analiza el Path Dependency (sendero dependencia) que modificó la anterior ausencia de los militares chilenos en los estados de excepción, especialmente, de catástrofes, entre el final de la dictadura (1990) hasta el terremoto de febrero de 2010. Desde entonces, las Fuerzas Armadas son actores fundamentales en una década llena de catástrofes naturales y la crisis social de 2019. Este sendero significa pasar de la desconfianza inicial del gobierno de la presidenta Bachelet, tras el sismo, hasta la actual cotidianidad con que las Fuerzas Armadas se asumen en estados de catástrofe o emergencia decretados sin grandes contratiempos por gobiernos de todos los signos políticos. A lo anterior debe sumarse la reforma más importante en un siglo en el Ministerio de Defensa Nacional y que coincidió con el terremoto.
High Tumoral KPNA2 Expression Is a Potential Biomarker for Poor Prognosis in Advanced Neuroblastoma Patients
Authors: OTAKE SAYAKA , OGUSHI KENJIRO , DORJKHORLOO GENDENSUREN , YOKOBORI TAKEHIKO , NISHI AKIRA , KUWANO HIROYUKI , SAEKI HIROSHI , SHIRABE KEN
Published: January 2025

Background/Aim: Karyopherin alpha 2 (KPNA2) has been reported to be associated with cancer aggressiveness and treatment resistance via transporting several cargo proteins into the nucleus, such as cancer-promoting E2F and DNA repair-related MRN complex. Recent studies have highlighted the KPNA2 functions in tumorigenesis and the progression of various cancers. However, the importance of KPNA2 expression has yet to be elucidated in clinical neuroblastoma patients. This study aimed to analyze the clinical impact of KPNA2 expression in neuroblastoma. Materials and Methods: KPNA2 expression in 81 resected neuroblastoma sections was examined using immuno-histochemical staining. The significance and prognostic value of tumoral KPNA2 expression were analyzed using our cohort and R2 database. Results: The KPNA2 was expressed in the nucleus of neuroblastoma cells. The expression level of nuclear KPNA2 was not associated with clinicopathological factors in neuroblastoma. Among our cohort (n=81), non-radically resected neuroblastoma patients (n=37) with high KPNA2 expression had poorer prognoses than those with low KPNA2 expression. The R2 database analysis validated that the high KPNA2 expression was related to the poor prognosis in the large-scale neuroblastoma cohort. Conclusion: KPNA2 expression evaluation in neuroblastoma is a promising indicator of prognosis in non-curative resected cases. KPNA2 targeting may be a promising therapeutic strategy against advanced neuroblastoma.
Complete Response (CR) in a Previously-progressing Chronic Lymphocytic Leukemia (CLL) Patient Treated With Methionine Restriction in Combination With First-line Chemotherapy
Authors: MORINAGA SEI , HAN QINGHONG , MIZUTA KOHEI , KANG BYUNG MO , YAMAMOTO NORIO , HAYASHI KATSUHIRO , KIMURA HIROAKI , MIWA SHINJI , IGARASHI KENTARO , HIGUCHI TAKASHI , TSUCHIYA HIROYUKI , DEMURA SATORU , HOFFMAN ROBERT M.
Published: January 2025

Background/Aim: Chronic lymphocytic leukemia (CLL) is currently incurable. CLL is characterized by disordered DNA methylation. The aim of the present study was to target methylation with methionine restriction in a patient with progressive CLL. Case Report: Methionine restriction for the patient was achieved with a low-methionine vegan diet and oral recombinant methioninase (o-rMETase). The patient also received rituximab, once per week for four weeks, and acalabrutinib 100 mg, twice daily (bid) continuously. The patient’s white blood cell count decreased by 95% from peak levels and extensive lymphadenopathy disappeared during combination treatment with o-rMETase, rituximab, and acalabrutinib. Conclusion: The combination of methionine restriction and first-line chemotherapy resulted in an apparent complete response (CR) in a CLL patient, a rare event. The duration of the CR will be monitored, and additional CLL patients will be treated similarly in the future.
Prostate Cancer Patient With Lymph-node Metastasis Treated Only With Methionine Restriction Has Stable Disease for Two Years Demonstrated With PET/CT and PSMA-PET Scanning and PSA Testing
Authors: MORINAGA SEI , HAN QINGHONG , MIZUTA KOHEI , KANG BYUNG MO , YAMAMOTO NORIO , HAYASHI KATSUHIRO , KIMURA HIROAKI , MIWA SHINJI , IGARASHI KENTARO , HIGUCHI TAKASHI , TSUCHIYA HIROYUKI , DEMURA SATORU , HOFFMAN ROBERT M.
Published: January 2025

Background/Aim: Metastatic prostate cancer is a recalcitrant disease. Our laboratory has previously treated prostate-cancer patients with methionine restriction effected by a low methionine diet and oral recombinant methioninase (o-rMETase), both alone and in combination with other agents. The present case is a 66-year-old patient who had a radical prostatectomy in 2019 with a Gleason score 3+3 and 3+4. The patient subsequently was treated with immunotherapy in 2021 and salvage proton-beam therapy in 2022, and subsequently treated only with o-rMETase and a low-methionine diet. The aim of the present study was to determine the long-term efficacy of methionine restriction on the patient's prostate cancer. Case Report: Starting in September 2022, the patient started methionine restriction with a low methionine-diet and o-rMETase, twice a day, after meals, at 250 units/dose. Since the start of methionine restriction, the patients’ prostate-specific antigen (PSA) has remained stable, under 2 ng/ml. Positron emission tomography/computed tomography (PET/CT) and prostate specific membrane antigen (PSMA)-PET imaging indicated in September 2023 a right pelvic-side-wall metastatic lymph node that was stable when the PSMA-PET scan was repeated in March 2024, with the standardized uptake value (SUV) decreasing from 19.39 to 14.98. A very small possible metastatic external-iliac lymph node was detected in March 2024. Thus, the lymph-node metastases were stable and did not increase. Conclusion: During the time the patient was on methionine restriction alone, effected by a low-methionine diet and o-rMETase, the metastatic prostate cancer did not progress. Further clinical studies of methionine restriction and metastatic prostate cancer are needed, including randomized clinical trials.
Effect of Diabetes on Outcomes in Patients With Incurable/Unresectable and Advanced/Recurrent Colorectal Cancer Receiving mFOLFOX6
Authors: IKEMURA MAI , HIRABATAKE MASAKI , ABURAYA MEGUMI , IKESUE HIROAKI , YASUI HISATERU , MUROI NOBUYUKI , HASHIDA TOHRU
Published: January 2025

Background/Aim: The high mortality rate associated with colon cancer in patients with diabetes is well-established; however, the underlying mechanisms have not been fully elucidated. Here, we investigated the efficacy of modified FOLFOX6 (mFOLFOX6) therapy, which is frequently used in colon cancer treatment, in patients with and without comorbid diabetes. Patients and Methods: The participants in this retrospective cohort study received mFOLFOX6 therapy as a first-line treatment for incurable/ unresectable and advanced/recurrent colon cancer. We compared patient background characteristics; number of mFOLFOX6 courses; total dose of each drug; reasons for dose reduction, deferment, or discontinuation; and survival time. Results: Data of six patients with diabetes and 26 without diabetes were assessed. There was no significant difference in background characteristics between the patient groups, with the exception of blood glucose levels. There was no significant difference in the planned number of mFOLFOX6 courses between the groups; however, the total number of completed courses was significantly lower in patients with diabetes than in those without diabetes. Discontinuation rates due to adverse events were similar between the groups; however, discontinuation due to progressive disease or death was significantly higher in patients with diabetes than in those without diabetes. No significant differences were observed in the total dose of each anticancer drug or survival time between the groups. Conclusion: mFOLFOX6 may not have sufficient therapeutic effects in patients with diabetes. Therefore, in patients with concurrent diabetes and colon cancer, alternative therapeutic options for cancer treatment should be considered.
Clinical and Pathological Analysis of Perianal Paget’s Disease: A Case Report and Review of 89 Cases
Authors: ISHII KAE , TAKAHASHI HIDEKAZU , TSUJI HIROMI , ISHIHARA TAKAYOSHI , IWAMI YUKA , JUAVIJITJAN WATSAPOL , YOKOTA MITSUKI , TAKAICHI SHOHEI , PAKU MASAKATSU , IWAMOTO KAZUYA , OHASHI TOMOFUMI , NAKAHARA YUJIRO , ASAOKA TADAFUMI , MATSUDA CHU , NISHIKAWA KAZUHIRO , OMORI TAKESHI
Published: January 2025

Background/Aim: Perianal Paget’s disease (PPD) is an intraepithelial invasion of the perianal skin that is frequently associated with anorectal carcinoma. Rectal canal carcinoma with Pagetoid spread (PS) is a relatively rare disease, and few reports on its outcomes are available. The relatively rare nature of this disease makes the development of treatment recommendations difficult. This study aimed to clarify the characteristics of the disease and factors related to prognosis. We present a case report and review of 89 cases, including those from the existing literature and our own experience. Case Report: The patient was an 81-year-old man who was referred to our hospital for surgery after endoscopic examination of the lower gastrointestinal tract revealed cancer of the anal canal with PS. Physical examination revealed erythema and erosions around the anus. Lower gastrointestinal endoscopy revealed an erythematous area and a continuous raised lesion in the anal canal. We diagnosed the patient with anal canal carcinoma with PS, and robot-assisted abdominoperineal resection was performed. Conclusion: Our findings indicate that the five-year survival rate for PPD patients was 63%, comparable to that of anal canal cancer without PS. The histological type and presence of lymph node metastasis may be related to the prognosis. The study suggests that early-stage patients with favorable histological types and no lymph node involvement may benefit from less invasive treatment options, such as endoscopic submucosal dissection.
Current Status of Sequential Treatment for Castration-resistant Prostate Cancer: A Retrospective Analysis
Authors: OSHINOMI KAZUHIKO , MUGITA TOSHIKI , INOUE TATSUKI , OMIZU MADOKA , YAMAGISHI MOTOKI , NAKAGAMI YOSHIHIRO , NAGATA MASAKAZU , SHIMOYAMA HIDEAKI , OTA MICHIYA , MORITA JUN , SASAKI HARUAKI , MATSUBARA EIJI , SAITO KATSUYUKI , FUJI KOHZO , MORITA MASASHI , FUKAGAI TAKASHI
Published: January 2025

Background/Aim: Although multiple treatments are available for metastatic castration-resistant prostate cancer, data to determine the optimal treatment sequence are limited. This study aimed to investigate the current status of drug therapy for castration-resistant prostate cancer and clarify the sequential treatment in actual clinical practice. Patients and Methods: This retrospective study included 425 patients diagnosed with castration-resistant prostate cancer at Showa University Hospital and affiliated hospitals between January 2014 and December 2021, who were treated with any of the following four drugs: novel androgen receptor signal inhibitors (abiraterone acetate and enzalutamide) and anticancer drugs (docetaxel and cabazitaxel). We investigated the actual treatment choices for castration-resistant prostate cancer, focusing on the order of administration of the four drugs. This analysis was visualized using a Sankey diagram. Results: Regarding the number of drugs administered, most patients received one type of drug, with androgen receptor signal inhibitors being the most commonly administered (total, 179; enzalutamide, 139 and abiraterone acetate, 40). Enzalutamide was the most frequently selected first-line drug (58.4%). The most common sequence for second-line treatment was androgen receptor signal inhibitor-androgen receptor signal inhibitor (n=96), followed by androgen receptor signal inhibitor-docetaxel (n=85), docetaxel-androgen receptor signal inhibitor (n=59), and docetaxel-cabazitaxel (n=6). Conclusion: Androgen receptor signal inhibitors is the most commonly used drug category for first-line treatment of castration-resistant prostate cancer, with enzalutamide being the most commonly used drug. Further investigations are required regarding patient background and prognosis.
Remnant Stomach Influx Reduces Esophageal Reflux and Malnutrition After Proximal Gastrectomy With Double Tract Reconstruction
Authors: NISHIGUCHI RYOHEI , SHIMAKAWA TAKESHI , ASAKA SHINICHI , OGAWA MASAKO , YAMAGUCHI KENTARO , MURAYAMA MINORU , SAGAWA MASANO , KUHARA KOTARO , USUI TAKEBUMI , YOKOMIZO HAJIME , SHIOZAWA SHUNICHI
Published: January 2025

Background/Aim: Remnant stomach influx (RSI) from the anastomotic jejunal-remnant stomach, a physiological food passage, develops after proximal gastrectomy with double-tract reconstruction (PGDT). Sometimes, food passes into the jejunal-loop (JL). We investigated the association of the food passage route in PGDT (RSI/JL) with postoperative esophageal reflux and malnutrition. Patients and Methods: We retrospectively collected data for 50 patients with upper-third gastric cancer and esophagogastric junction cancer with PGDT. Using one-year postoperative fluoroscopy findings, 40 propensity score-matched patients were classified into RSI and JL groups (n=20/group), respectively. The groups were comparatively evaluated for: clinicopathological characteristics [age, sex, body mass index (BMI), visceral fat index (VFI), subcutaneous fat index (SFI), skeletal muscle index, pathological stage]; perioperative factors [approach, postoperative complications ≥ Clavien-Dindo Grade 2, postoperative food passage); and esophageal reflux (reflux esophagitis frequency ≥ Grade A, degree of reflux based on fluoroscopy findings). Univariate and multivariate analysis identified predictive factors for post-operative malnutrition in all 50 patients. Results: After propensity score matching, grade of reflux esophagitis and degree of reflux was significantly lower (p=0.014, p<0.001) in the RSI versus JL group. The RSI group showed significantly attenuated percent decrease in BMI, VFI, and SFI (p=0.049, p=0.002, p=0.006). Multivariate analysis identified food passage route (JL) and pathological stage as predictive factors for postoperative malnutrition. Conclusion: Postoperative esophageal reflux and malnutrition were attenuated by food passage mainly via the RSI after PGDT. Improved jejunal-remnant stomach is requisite to ensure satisfactory remnant stomach influx.
Treatment Strategies in Elderly Patients With Operable, Hormone Receptor-negative Breast Cancer
Authors: IKEDA TATSUHIKO , TAKEDA MISUZU , TSUJI MUNECHIKA , AKATSUKA SOTARO , OTA DAISUKE
Published: January 2025

Background/Aim: Elderly patients with early-stage breast cancer have potentially been underrepresented in clinical trials. Thus, treatment strategies for a minority of elderly patients with hormone receptor (HR)-negative breast cancer may be inadequately informed. Patients and Methods: We retrospectively reviewed 126 patients with HR-negative breast cancer aged ≥65 years. Patients aged ≥75 years (group A) were compared with those aged 65-74 years (group B). Of the 126 surgically treated patients, 48 were in group A and 78 were in group B. Results: The number of patients who did not undergo axillary lymph node surgery was significantly higher in group A than that in group B (15% vs. 2%, respectively, p=0.047). The number of patients who received radiotherapy was significantly lower in group A than B (13% vs. 44%, respectively, p<0.01). The number of patients who did not receive chemotherapy was significantly higher in group A than B (79% vs. 23%, respectively, p<0.01). Breast cancer-specific survival and overall survival showed no significant difference between groups. Conclusion: Omission of axillary surgery, radiation, or chemotherapy may not have a significant prognostic impact in patients with HR-negative breast cancer aged ≥75 years. Multiple age-related factors complicate the standardization of optimal treatment decisions for these patients.
Prognostic Value of the Modified Cachexia Index in Colorectal Cancer Patients Undergoing Curative Surgery
Authors: NISHIYAMA TSUYOSHI , SHIBUTANI MASATSUNE , TANDA HIDEKI , SEKI YUKI , KASHIWAGI SHINICHIRO , KASASHIMA HIROAKI , FUKUOKA TATSUNARI , MAEDA KIYOSHI
Published: January 2025

Background/Aim: The cachexia index (CXI) has been reported to be a useful indicator for predicting the prognosis of cancer patients. However, CXI calculation requires skeletal muscle index (SMI) measurements, which involves an analysis of computed tomography images using an imaging software program, which makes the calculation process highly complex and time-consuming. Recently, the modified cachexia index (mCXI), calculated using the urea-to-creatinine ratio (UCR) instead of SMI, has been reported to be a useful marker that is easier to calculate than CXI. This study aimed to evaluate the correlation between mCXI and the prognosis of patients with colorectal cancer (CRC). Patients and Methods: A total of 291 patients who underwent curative surgery for stage I-III CRC were enrolled. mCXI was calculated as the serum albumin concentration/neutrophil-to-lymphocyte ratio (NLR)/UCR. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value of the mCXI for predicting prognosis. Results: The median mCXI was 0.089 (range=0.012-0.354). The ROC curve analysis revealed that the appropriate cut-off value for mCXI was 0.113. The low mCXI group had significantly shorter relapse-free and overall survival rates than the high mCXI group (p=0.030 and p=0.014, respectively). Conclusion: mCXI, which does not require an image analysis, may be closely associated with prognosis in patients undergoing curative surgery for CRC.
Association of Pretreatment Albumin-bilirubin Grade With Hepatotoxicity and Efficacy in EGFR-TKIs Therapy for NSCLC
Authors: ARIHARA HIROKI , NAGAMATSU HIDETSUGU , HAYAKAWA YUJI , MASE HIROKI , ARAYA TOMOYUKI , KITA TOSHIYUKI
Published: January 2025

Background/Aim: The albumin-bilirubin (ALBI) grade is an assessment tool for hepatic function and prognosis in patients with hepatocellular carcinoma (HCC). However, its significance in patients with non-small cell lung cancer (NSCLC) treated with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) remains unclear. We retrospectively investigated the relationship between pre-treatment ALBI grade and hepatotoxicity and treatment efficacy in patients with NSCLC receiving EGFR-TKIs. Patients and Methods: We analyzed data from 182 patients with NSCLC treated with EGFR-TKIs. Patients were categorized into ALBI grades 1/2a and 2b/3 groups. We examined the association between ALBI grade, hepatotoxicity, and time to treatment failure (TTF) using univariate and multivariate analyses. Results: In the univariate Kaplan-Meier analysis, ALBI grade was not associated with hepatotoxicity (log-rank p=0.56). This finding was consistent with the multivariate analysis of patients treated with gefitinib and erlotinib (n=158). However, In the univariate Kaplan-Meier analysis, the median TTF for the ALBI grade 1/2a group was 10.6 months, compared to 5.8 months for the ALBI grade 2b/3 group (hazard ratio=1.66, 95% confidence interval=1.19-2.33, p=0.003). Multivariate analysis confirmed that ALBI grade 2b/3 (hazard ratio=1.64, 95% confidence interval=1.16-2.30, p<0.01) was independently associated with shortened TTF. Conclusion: Pretreatment ALBI grade classification can predict efficacy in patients with NSCLC treated with EGFR-TKIs.
Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study
Authors: Rubaiat Rahmina , Templeton John Michael , Schneider Sandra L , De Silva Upeka , Madanian Samaneh , Poellabauer Christian
Published: January 2025

Background

Speech features are increasingly linked to neurodegenerative and mental health conditions, offering the potential for early detection and differentiation between disorders. As interest in speech analysis grows, distinguishing between conditions becomes critical for reliable diagnosis and assessment.

Objective

This pilot study explores speech biosignatures in two distinct neurodegenerative conditions: (1) mild traumatic brain injuries (eg, concussions) and (2) Parkinson disease (PD) as the neurodegenerative condition.

Methods

The study included speech samples from 235 participants (97 concussed and 94 age-matched healthy controls, 29 PD and 15 healthy controls) for the PaTaKa test and 239 participants (91 concussed and 104 healthy controls, 29 PD and 15 healthy controls) for the Sustained Vowel (/ah/) test. Age-matched healthy controls were used. Young age-matched controls were used for concussion and respective age-matched controls for neurodegenerative participants (15 healthy samples for both tests). Data augmentation with noise was applied to balance small datasets for neurodegenerative and healthy controls. Machine learning models (support vector machine, decision tree, random forest, and Extreme Gradient Boosting) were employed using 37 temporal and spectral speech features. A 5-fold stratified cross-validation was used to evaluate classification performance.

Results

For the PaTaKa test, classifiers performed well, achieving F1-scores above 0.9 for concussed versus healthy and concussed versus neurodegenerative classifications across all models. Initial tests using the original dataset for neurodegenerative versus healthy classification yielded very poor results, with F1-scores below 0.2 and accuracy under 30% (eg, below 12 out of 44 correctly classified samples) across all models. This underscored the need for data augmentation, which significantly improved performance to 60%‐70% (eg, 26‐31 out of 44 samples) accuracy. In contrast, the Sustained Vowel test showed mixed results; F1-scores remained high (more than 0.85 across all models) for concussed versus neurodegenerative classifications but were significantly lower for concussed versus healthy (0.59‐0.62) and neurodegenerative versus healthy (0.33‐0.77), depending on the model.

Conclusions

This study highlights the potential of speech features as biomarkers for neurodegenerative conditions. The PaTaKa test exhibited strong discriminative ability, especially for concussed versus neurodegenerative and concussed versus healthy tasks, whereas challenges remain for neurodegenerative versus healthy classification. These findings emphasize the need for further exploration of speech-based tools for differential diagnosis and early identification in neurodegenerative health.
Evaluation of a Global Initiative for Asthma Education and Implementation Program to Improve Asthma Care Quality (CARE4ALL): Protocol for a Multicenter, Single-Arm Study
Authors: Huang Kewu , Wang Wenjun , Wang Ying , Li Yanming , Feng Xiaokai , Shen Huahao , Wang Chen
Published: January 2025

Background

Poor symptom control and exacerbations of asthma diminish quality of life and pose a significant burden to patients and society. Implementing evidence-based management as recommended by the Global Initiative for Asthma (GINA), especially introducing inhaled corticosteroid–containing treatments, has the potential to vastly reduce exacerbations and the high burden of asthma in China. However, domestic implementation of the GINA recommendations has been unsatisfactory, especially in lower-level hospitals; thus, an enhancement to the awareness of and adherence to the GINA recommendations among Chinese physicians is needed to improve patient outcomes.

Objective

This study aims to bridge the gap between the GINA recommendations and the current clinical practice in China by demonstrating the benefits of an asthma quality improvement program (QIP).

Methods

A single-arm study will be conducted at around 30 hospitals across China to assess the impact of a specially designed asthma QIP. Approximately 1500 patients with asthma aged ≥14 years will be enrolled in participating hospitals and followed up for 48 weeks. The QIP—targeted at all pulmonologists and specialist nurses—will include an initial comprehensive training (including a pretraining questionnaire and posttraining quizzes) provided by a dedicated, qualified training team based on the GINA 2021 recommendations, followed by regular reinforcement learnings (integrated into the regular department lectures delivered by department directors), with multiple offline and online approaches (eg, an online patient management platform) provided as supportive tools. During this study, GINA implementation performance will be continuously monitored to inform necessary adjustments at the hospital level. The primary end point is change from baseline in the proportion of participants with an inhaled corticosteroid–based maintenance or reliever treatment at week 48. Secondary end points and exploratory end points include changes in clinical practice and patient outcomes such as treatment patterns, asthma control, and hospitalization rates due to exacerbations.

Results

This study has been completed, with 1500 patients enrolled and 1271 patients completing the study. The last visit of the last patient was on September 3, 2024, and the database lock was on September 28, 2024. Final analysis of data has started in October 2024.

Conclusions

The Change Asthma Clinical Practice through GINA Education and Implementation for All Patients With Asthma (CARE4ALL) study will hopefully help improve asthma management and patient outcomes in China by bridging the gap between evidence-based GINA recommendations and the current clinical practice.

Trial Registration

ClinicalTrials.gov NCT05440097; https://clinicaltrials.gov/study/NCT05440097

International Registered Report Identifier (IRRID)

DERR1-10.2196/65197
Traditional Medicinal Plants for the Prevention and Treatment of Hypertension: A Literature Review
Authors: Febyanesti Athika Reza , Widjanarko Bagoes , Shaluhiyah Zahroh
Published: January 2025

Background: Hypertension is described as a disease that has a high prevalence in Indonesia. If it is not appropriately treated, it will cause advanced diseases such as stroke, heart failure, and kidney damage. Therefore, it is necessary to prevent and give early treatment, one of which is through alternative routine consumption of herbal medicines.Objectives: This study aims to find out the benefits of herbal medicine for people with hypertension.Methods: The method used in this research is a literature review. It is carried out in several stages by analyzing relevant previous pieces of literature using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) flowchart that illustrates the flow of information through the different phases of a systematic review.Results: A total of 11 reviewed articles show that various herbal plants were obtained with multiple uses to reduce hypertension, and these plants were easy to get and use. It shows that the boiled leaves were the most frequently used part of the plant. Herbal treatment for hypertension aims to enrich antioxidants, block calcium channels, strengthen the endothelium, inhibit ACE, increase without production, and release and decrease biogenic amines. Herbal plants like lemongrass leaves, ginger, gotu kola leaves, and cat's whiskers are useful for lowering blood pressure levels in routine and intensive use without any side effect intervention by boiling.Conclusion: Education regarding herbal plants for hypertension is also beneficial because the increased insight and knowledge they have reduced the possibility of hypertension occurring in the community
PENGARUH WAKTU TUNGGU TERHADAP KEPUASAN PASIEN DI UNIT RAWAT JALAN (POLI PENYAKIT DALAM) DI RSD IDAMAN BANJARBARU TAHUN 2024
Authors: Wildan Muhammad Wildan
Published: January 2025

ABSTRACTPatient satisfaction is a level of feeling that arises as a result of the performance of health servicesobtained after being compared with expectations. The aim of this research is to determine the effectof waiting time on patient satisfaction in the outpatient unit (internal medicine clinic) at RSD IdamanBanjarbaru in 2024. The method used is a quantitative method with a cross sectional design. Datacollection was carried out using a questionnaire. The results of this study show that there is noinfluence between patient satisfaction and the waiting time for TPPRJ services at RSD IdamanBanjarbaru in 2023 with p-value = 0,372 > 0,05.Keywords: Waiting Time, Patient SatisfactionABSTRAKKepuasan pasien merupakan suatu tingkat perasaan yang muncul sebagai akibat dari kinerja layanankesehatan yang diperoleh setelah membandingkan dengan harapan. Tujuan dari penelitian ini adalahuntuk mengetahui pengaruh waktu tunggu terhadap kepuasan pasien di unit rawat jalan (poli penyakitdalam) di RSD Idaman Banjarbaru tahun 2024. Metode yang digunakan ialah metode kuantitatifdengan desain cross sectional. Pengumpulan data dilakukan dengan cara menggunakan kuesioner.Hasil penelitian ini menunjukan bahwa tidak terdapat pengaruh antara kepuasan pasien denganWaktu Tunggu Layanan TPPRJ di RSD Idaman Banjarbaru tahun 2023 dengan p-value = 0,372 >0,05.Kata Kunci : Waktu Tunggu, Kepuasan Pasien
Cytotoxic Activity of Ethanol Extract of Piper aduncum L. on T47D Breast Cancer Cell Line using the MTT Method
Authors: Bellatasie Rezlie , Oktavia Sri , Rakhmil Hanaya Fathiha , Uyun Hendri Satria Kamal
Published: January 2025

Cancer treatment is known to cause side effects ranging from mild to severe, which can also affect the quality of the patient's health. Natural ingredients are an alternative source of cytotoxic substances with good anticancer activity and minimum side effects. Sirih hutan (Piper aduncum L.), also known as spiked pepper, is a medicinal plant with potential cytotoxic activity. This study aims to determine the cytotoxic activity of the ethanol extract of P. aduncum L. leaves with the Microculture Tetrazolium Test method. Phytochemical screening showed that P. aduncum L. contains alkaloids, flavonoids, saponin, phenol, and steroid/terpenoid compounds. The cytotoxic activity test was carried out on T47D cells with a concentration of 100 µg/mL, 10 µg/mL, 1 µg/mL, and 0.1 µg/mL test solution. The obtained IC50 value of the ethanol extract of P. aduncum L. was 171.2 µg/mL, belonging to the moderate toxic category. From this study, it is concluded that P. aduncum L holds potential as an anticancer agent.
Formulation and Physical Evaluation of Orthosiphon aristatus Leaf Extract Granule Preparation as Herbal Beverage Candidate
Authors: Al-Hakim Nur Achsan , Nur Fauziyyah Salma Alifia , Purnamasari Nira , Faramayuda Fahrauk
Published: January 2025

Developing Orthosiphon aristatus (Blume) Miq. leaf extract of purple varieties into granule dosage forms is expected to facilitate consumption, storage, and can extend the shelf life of the product. This study aims to develop the formulation and evaluation of granule preparations of O. aristatus leaf extract of purple varieties, with a comparison of lactose and maltodextrin fillers to produce the best formula. The granule dosage forms were prepared using wet granulation method. Furthermore, the variation of granule preparation formula consists of F1 (extract with lactose), F2 (extract with maltodextrin), F3 (extract with a combination of lactose and maltodextrin 1:1), F4 (freeze dried extract with lactose), F5 (freeze dried extract with maltodextrin), and F6 (freeze dried extract with a combination of lactose and maltodextrin 1:1). The physical evaluation of granules comprised moisture content testing, flowability, compressibility index, particle size distribution, and granule dissolving time. Results from the physical evaluation of granules over 28 days of storage indicated that all six formulas met the criteria for good granules, with F3 emerging as the optimal formula due to its superior physical stability and visually appealing appearance upon dissolution. To conclude, this study demonstrates that O. aristatus leaf extract can be effectively formulated into instant granule preparations suitable for herbal beverage or alternative medicine. Moreover, by modifying the filler material, the physical stability of the granule preparation can be maintained.