bluuebunny/crossref_metadata_2025 huggingface dataset:
SISTEM PENDAJADWALAN DOKTER DAN FASILITAS POLI PADA RUMAH SAKIT SULTAN ISKANDAR MUDA NAGAN RAYA BERBASIS ANDROID MENGGUNAKAN FLUTTER
Authors: Payana Mahendar Dwi , Musliyana Zuhar , Ardian Zalfie , Wibawa M Bayu , TB Desita Ria Yusian
Published: August 2023

Abstrak— Penyajian informasi jadwal praktek dokter dan poli pada Rumah Sakit Sultan Iskandar Muda Nagan Raya selama ini masih belum terpublikasi dengan bauk kepada masyarakat. Untuk mengetahui jadwal dokter dan poli masyarakat mengharuskan diri ke rumah sakit langsung. Permasalahan pada informasi yang diberikan pihak Rumah Sakit khususnya pada website yang tersedia tidak adanya informasi jadwal dokter, jadwal poli. Dengan adanya teknologi informasi berupa aplikasi, nantinya masyarakat bisa mengetahui dengan akurat jadwal dokter dan fasilitas kesehatan yang tersedia di Rumah Sakit Sultan Iskandar Muda. Masyarakat tidak perlu datang langsung ke Rumah Sakit apabila hanya sekedar untuk mengetahui jadwal dokter dan fasilitas kesehatan yang tersedia. Guna mengatasi permasalahan tersebut dibutuhkan sebuah sistem yang dapat memberikan informasi terkait dengan jadwal dokter dan fasilitas yang ada pada Rumah sakit tersebut secara online. Teknologi yang digunakan pada sistem ini nantinya berbasis websiste di sisi admin dan android pada bagian pengguna atau masyarakat. Teknologi yang digunakan untuk membangun aplikasi android menggunakan bahasa pemrograman dart dengan framework flutter. Informasi yang disajikan dari aplikasi ini berupa jadwal dokter dan fasilitas baik poliklinik, dan sebagainya yang tersedia pada Rumah Sakit Sultan Iskandar Muda.Kata Kunci : Android, jadwal dokter, fasilitas rumah sakit, kesehatan, flutterAbstract—The presentation of doctor and polyclinic schedule information at Sultan Iskandar Muda Nagan Raya Hospital has not been effectively communicated to the public. To obtain doctor and polyclinic schedules, people are required to visit the hospital directly. The problem lies in the lack of information provided by the hospital, particularly on their website, where there is no information about doctor schedules or polyclinic schedules. With the use of information technology in the form of an application, the public will be able to accurately access the schedules of doctors and healthcare facilities available at Sultan Iskandar Muda Hospital. People will no longer need to visit the hospital just to find out about doctor schedules and available healthcare facilities. To address this issue, a system is needed that can provide online information regarding doctor schedules and available facilities at the hospital. The technology used in this system will be based on a website for the admin side, and on Android for the user or public side. The technology used to develop the Android application will involve the Dart programming language with the Flutter framework. The information provided by this application will include doctor schedules and various facilities, such as the polyclinic, available at Sultan Iskandar Muda Hospital.Keywords : Android, doctor schedule, hospital fasility, health, flutter
OPTIMASI KINERJA MIKROTIK TERHADAP SERANGAN BRUTE FORCE DAN DDOS
Authors: Sayuti M , Gunawan Doni
Published: August 2023

Abstrak— Serangan суbеr уаng semakin meningkat mеnjаdіkаn реrѕоаlаn bagi реnуеdіа layanan jasa internet. Contoh jenis ѕеrаngаn суbеr yang digunakan аdаlаh dеngаn tеknіk serangan DDoS dаn Brute Fоrсе. Pеrаngkаt jaringan ѕереrtі Mikrotik pun bisa mеnjаdі target dari ѕеrаngаn. Uрауа mencegah serangan dіреrlukаn dеngаn ѕuаtu ѕіѕtеm keamanan. Pеnеlіtіаn ini mеnggunаkаn mеtоdе kuаntіtаtіf dеngаn menganalisis реrfоrmаѕі dаn kіnеrjа dаrі Mіkrоtіk apabila tеrjаdі ѕеrаngаn. Hаѕіl Pеngujіаn, serangan DDos sebanyak 171847 ѕеrаngаn ke port 80 terpantau CPU Mikrotik ѕеbеѕаr 96,81% dаn раdа wеbѕеrvеr ѕеbеѕаr 16,61%. Pеrаngkаt Mikrotik уаng tеlаh terkena ѕеrаngаn DDoS ѕudаh tidak dараt lagi bеrореrаѕі secara nоrmаl. Namun saat ѕkеnаrіо  ѕеrаngаn  Brute  Force,  tеrраntu  nоrmаl  4,76%  раdа  CPU  Mikrotik  kаrеnа  роrt fоrwаrdіng telah mеnеruѕkаn раkеt ѕеrаngаn kе ѕеrvеr Hоnеуроt. Kesimpulan dari реnеlіtіаn іnі serangan DDoS dan Brutе Fоrсе mengakibatkan реnіngkаtаn bеbаn kіnеrjа CPU baik раdа Mikrotik mаuрun pada ѕеrvеr Hоnеуроt.Kata kunci: Mikrotik, Brute Force, DDos, ServerAbstract— Increasing суbеr аttасkѕ hаvе become a рrоblеm fоr іntеrnеt ѕеrvісе providers. Exаmрlеѕ оf tуреѕ of суbеr аttасkѕ uѕеd аrе DDoS and Brute Fоrсе attack tесhnіԛuеѕ. Nеtwоrk dеvісеѕ ѕuсh аѕ Mіkrоtіk саn аlѕо become targets of attacks. Effоrtѕ tо рrеvеnt аttасkѕ аrе needed with a security system. Thіѕ rеѕеаrсh uѕеѕ quantitative mеthоdѕ bу аnаlуzіng thе реrfоrmаnсе and performance оf Mіkrоtіk in the еvеnt of аn аttасk. Tеѕt rеѕultѕ, DDоѕ attacks as mаnу as 171847 аttасkѕ оn port 80 monitored bу CPU Mikrotik by 96.81% аnd оn the wеbѕеrvеr bу 16.61%. Mіkrоtіk  devices  that  hаvе  bееn  hіt  bу  a  DDоS  аttасk  can  nо  lоngеr  ореrаtе  normally. Hоwеvеr, durіng thе Brutе Force attack scenario, nоrmаl 4.76% ѕuрроrtѕ the Mіkrоtіk CPU bесаuѕе  роrt  fоrwаrdіng  hаѕ  fоrwаrdеd  thе  аttасk  расkеt  to  the  Hоnеуроt  ѕеrvеr.  Thе соnсluѕіоn оf this study DDоS аnd Brute Force attacks rеѕultеd in an іnсrеаѕе in thе CPU реrfоrmаnсе load bоth оn Mіkrоtіk and оn thе Hоnеуроt server.Keywords: Mikrotik, Brute Force, DDos, Server
Pengaruh Teknik Alternate Nostril Breathing Terhadap Tekanan Darah Pada Lansia Dengan Hipertensi
Authors: Ramadhan Yasinta Ciptanti , Prajayanti Eska Dwi
Published: August 2023

Lansia adalah seseorang yang telah mencapai usia 60 tahun ke atas. Lansia mengalami penurunan fisiologis yang mempengaruhi pembuluh darah dan mengakibatkan hipertensi Penelitian ini bertujuan untuk mengetahui pengaruh Teknik Alternate Nostril Breathing terhadap tekanan darah pada lansia dengan hipertensi. Desain penelitian ini yaitu quasi ksperimen dengan rancangan penelitian One Group Pretest-postest Design. Lokasi dalam penelitian ini adalah di Kelurahan Kedungwaduk, Kecamatan Karangmalang, Kabupaten Sragen. Penelitian ini dilaksanakan pada bulan Juli. Populasi yang digunakan pada penelitian ini adalah lansia hipertensi. Jumlah populasi hipertensi di Kelurahan Kedungwaduk yaitu 102 dengan jumlah sampel 50 orang. Analisa data yang dilakukan Analisa univariat dan Analisa bivariat. Hasil penelitian yang didapatkan ialah tekanan darah lansia sebelum di lakukan teknik alternate nosril breathing terhadap tekanan darah pada lansia dengan hipertensi hasil tekanan darah kategori mayoritas adalah kategori hipertensi ringan yaitu 38 orang (69,1%). Tekanan darah lansia sesudah di lakukan teknik alternate nosril breathing terhadap tekanan darah pada lansia dengan hipertensi hasil tekanan darah kategori mayoritas adalah kategori hipertensi ringan yaitu 37 orang (67,3%). Ada Pengaruh pemberian intervensi dengan teknik alternate nosril breathing terhadap tekanan darah pada lansia dengan hipertensi di Kelurahan Kedungwaduk, Kabupaten Sragen.
Gambaran Skala Nyeri Haid (Dismenorea) Pada Remaja Putri Di Desa Tanjungrejo Kabupaten Sukoharjo
Authors: Putri Iiq Widowati Suryaning , Gati Norman Wijaya
Published: August 2023

Dismenore merupakan kondisi yang terjadi saat menstruasi, yang dapat mengganggu aktivitas dan memerlukan penanganan ditandai dengan rasa sakit atau nyeri hebat pada perut atau panggul. Tujuan penelitian mengetahui gambaran skala nyeri haid (dismenorea) pada remaja putri di Desa Tanjungrejo Kabupaten Sukoharjo. Penelitian ini menggunakan metode deskriptif kuantitatif desain non analitik, dengan pendekatan cross sectional. Populasi dalam penelitian ini berjumlah 155 remaja putri dengan total sampel sebanyak 61 responden, teknik sampling dengan purposive sampling. Pengumpulan data menggunakan lembar kuesioner pengukuran skala nyeri Numeric Rating Scale (NRS). Analisa data menggunakan metode univariat berupa statistik deskriptif. Hasil analisis univariat menunjukkan bahwa sebagian besar karakteristik responden berdasarkan usia berada pada remaja akhir dengan rentang usia 16-19 tahun sebanyak 29 orang (47,5%), sebagian besar mengalami menarche normal pada usia 12-13 tahun sebanyak 47 orang (77,0%), skala nyeri haid (dismenorea) nyeri sedang terdiri dari 28 responden (45,9%). Direkomendasikan penelitian selanjutnya untuk menghubungkan variabel lain atau yang berkaitan dengan nyeri haid remaja
UI/UX Analysis of Project Management Information System (PMIS) Website Using User-Centered Design Method
Authors: Azhar Sarah Afifah , Defriani Meriska , Hermanto Teguh Iman
Published: August 2023

In Industry 4.0, a lot of data has been digitized and is no longer stored manually. In helping to record all the projects that were worked on initially stored in outstanding Project Management applications such as Trello. However, the Trello application has limitations and compatibility with business processes, including employees not writing down projects that have been done because they are not in accordance with procedures, causing many projects to go unrecorded. So because of these limitations a Project Management Information System (PMIS) website is needed which makes it easy to record all projects so that there is no more unrecorded data. Furthermore, there are problems in conducting an analysis that can make it easier for users and how to design a User Interface and User Experience on the PMIS website using the User Centered Design (UCD) method, which in the manufacturing process will continue to make changes according to needs. The results of the User Interface design that has been made will be tested for User Experience using the Single Ease Questionnaire (SEQ) method as a measure of the success of the User Interface that has been made. Based on the results of the User Experience test using the Single Ease Questionnaire method for 5 respondents, an average value of 6.3 was obtained, which means that it can be concluded that the User Interface that has been created has a level of convenience that is in accordance with the User Experience.
Different Types of Business (Especial emphasis on business structure of Bangladesh)
Authors: Yousuf Mohammad Asad Bin
Published: August 2023

Business has become an inevitable part of human living. In era of globalization business is the most widely used term which was derived from the word busy. Business typically means being occupied with any occupation to produce, purchase, sell or serve society in order to make a earn of living. It is being estimated that the evolution of Business started in 1500 AD, few historiographers claim business is 3000 years old. No matter how old business is, with change of time business model, types and structure have been improvised across globe. Today’s dynamic business world comprise of multiple business structures to meet unique demand of societies. Bangladesh has no exception to that. Several business structures have been adopted by the people of this subcontinent. This article talks about different business structure of today’s business world and their benefits. Reader knowledge will be enhanced further about different business structures.
Prevalence of antecedent Kawasaki disease in young adults with suspected acute coronary syndrome in high incidence cohort
Authors: Shyu Tsung-Cheng , Wu Chiung-Jen , Fu Yun-Ching , Peng Yi-Chin , Chuang Tzu-Yao , Kuo Ho-Chang , Hsieh Kai-Sheng , Tai I-Hsin
Published: August 2023

Background

Acute coronary syndrome (ACS) in early adulthood (<40 years old) may be associated with unrevealed diagnoses of Kawasaki disease (KD) in childhood. Daniels et al. showed that 5% of young adults with acute coronary syndrome might have antecedent Kawasaki disease in a cohort with Kawasaki disease incidence rates ranging from about 9 to 20 per 100,000 children under 5 years of age. However, there is no relevant research from the cohort with higher incidence rates (>80–100 per 100,000 children under 5 years of age) of Kawasaki disease.

Methods

We conducted a multicenter, retrospective study by reviewing medical records and angiographic data from two institutions (middle and southern Taiwan, respectively) of adults <40 years of age who underwent coronary angiography for clinically suspected acute coronary syndrome (2009–2019). Angiographic images were independently analyzed by three cardiologists who were blinded to the medical records. Demographic and laboratory data and risk factors of coronary artery disease were integrated to assess the likelihood of antecedent KD.

Results

All 323 young adults underwent coronary angiography, and 27 had coronary aneurysms. The patients’ clinical and angiographic characteristics were evaluated, and 7.4% had aneurysms likely to be associated with KD. Most subjects were male (23/24), and their low-density lipoprotein (LDL) levels were significantly higher (p = 0.028) than those of subjects unlikely to have KD.

Conclusion

This study proposed that the cohort with higher Kawasaki disease incidence rates may have a higher prevalence of young adult ACS associated with antecedent KD. The importance of determining the clinical therapeutic significance of antecedent Kawasaki disease in young adult ACS warrants advanced research. Higher LDL levels may have a long-term cardiovascular impact in KD patients with persistent coronary aneurysms.
Biometric linkage of longitudinally collected electronic case report forms and confirmation of subject identity: an open framework for ODK and related tools
Authors: Roberts Chrissy h. , Stott Callum , Shawe-Taylor Marianne , Chaudhry Zain , Lal Sham , Marks Michael
Published: August 2023

The availability of low-cost biometric hardware sensors and software makes it possible to rapidly, affordably and securely sample and store a unique and invariant biological signature (or biometric “template”) for the purposes of identification. This has applications in research and trials, particularly for purposes of consent, linkage of case reporting forms collected at different times, and in the confirmation of participant identity for purposes of safety monitoring and adherence to international data laws. More broadly, these methods are applicable to the needs of the billion people who live in resource-restricted settings without identification credentials. The use of mobile electronic data collection software has recently become commonplace in clinical trials, research and actions for public good. A raft of tools based on the open-source ODK project now provide diverse options for data management that work consistently in resource-restricted settings, but none have built-in functionality for capturing biometric templates. In this study, we report the development and validation of a novel open-source app and associated method for capturing and matching biometric fingerprint templates during data collection with the popular data platforms ODK, KoBoToolbox, SurveyCTO, Ona and CommCare. Using data from more than 1,000 fingers, we show that fingerprint templates can be used to link data records with high accuracy. The accuracy of this process increases through the linkage of multiple fingerprints to each data record. By focussing on publishing open-source code and documentation, and by using an affordable (<£50) and mass-produced model of fingerprint sensor, we are able to make this platform freely available to the large global user community that utilises ODK and related data collection systems.
Evaluation of cardiovascular toxicity of the atezolizumab and bevacizumab combination
Authors: Niimura Takahiro , Goda Mitsuhiro , Miyata Koji , Matsumoto Jun , Yoshioka Toshihiko , Hamano Hirofumi , Aizawa Fuka , Yagi Kenta , Izawa-Ishizawa Yuki , Zamami Yoshito , Ishizawa Keisuke
Published: August 2023

Introduction: The combination of atezolizumab, an immune checkpoint inhibitor (ICI), and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is the first choice for systemic therapy in hepatocellular carcinoma. Immune-related cardiovascular toxicity—myocarditis and pericarditis—are known to occur during ICI treatment. By contrast, VEGF inhibitors (VEGFIs) cause cardiovascular complications such as hypertension and heart failure. Thus, different cardiovascular toxicities have been recognized for ICIs and VEGFIs, but the impact of their combination remains unclear. Here, we aimed to investigate the cardiovascular toxicity profile of atezolizumab in combination with bevacizumab using the World Health Organization adverse event reporting database—VigiBase.

Methods: We analyzed data included in VigiBase till December 2022. To evaluate the frequency of reports related to atezolizumab, bevacizumab, and their combinations for 21 adverse events, we calculated the reporting odds ratio and information component. Analyses of the fatality of various cardiovascular toxicities associated with the use of each drug were performed.

Results: The database included 84,951, 10,595, and 2,092 reports of treatment with bevacizumab, atezolizumab, and their combination, respectively. The disproportionality signal of hypertension, arterial embolism and thrombosis, supraventricular tachyarrhythmias, heart failure, myocarditis, hemorrhage-related clinical events, venous embolism and thrombosis, cardiomyopathy, respiratory failure with combination regimen of atezolizumab and bevacizumab was detected. Signals of these adverse events were also detected treatment with either atezolizumab or bevacizumab alone. Venous embolism and thrombosis exhibited the highest fatality rate in the two drug combination (12.82%) relative to those of atezolizumab (6.19%) and bevacizumab (4.54%).

Discussion: Cardiovascular toxicity, owing to the combination of atezolizumab and bevacizumab, was similar to that of each single agent, and no new safety concerns were observed. Caution should be exercised when combining the two drugs since the fatality rate of thromboembolism increases with combination treatment.
Constraints on the structure of the oceanic crust of the Tamu Massif by teleseismic P-wave coda autocorrelation
Authors: Xu Fucong , Lu Shaoping , Cai Chen , Chen Han , Dong Shaozhe
Published: August 2023

The Tamu Massif, considered the biggest single volcano on Earth, was formed by the accumulation of enormous amounts of magma erupting to the surface. It is the largest and oldest seamount in Shatsky Rise, which is the third largest oceanic plateau on Earth. However, the formation mechanism of Tamu Massif is still controversial because evidence point to different formation hypotheses. In this paper, we applied the P-wave coda autocorrelation method and used the hydrophone waveform data acquired by the ocean bottom seismometer (OBS) deployed on Tamu Massif to constrain the oceanic crust, and these results provide new finding on the structure of the oceanic crust for Tamu Massif. We hope it can provide some implications to research the formation mechanism of Tamu Massif. These results show that some stations in Tamu Massif received reflection signals from shallower depths that are nearly parallel to the seafloor. We infer that in the shallow oceanic crust, there is a layer composed of alternating eruptions of dense, higher velocity massive lava and sparse, lower velocity pillow lava flows, which have less density and lower velocity compared to the lower oceanic crust, with a strong acoustic impedance contrasts between them and thus able to generate a reflection signal, which is observed in our autocorrelation results.
Role of irisin in bone diseases
Authors: Zhao Ruobing , Chen Yan , Wang Dongxue , Zhang Chunyu , Song Henan , Ni Guoxin
Published: August 2023

Bone diseases are common among middle-aged and elderly people, and harm to activities of daily living (ADL) and quality of life (QOL) for patients. It is crucial to search for key regulatory factors associated with the development of bone diseases and explore potential therapeutic targets for bone diseases. Irisin is a novel myokine that has been discovered in recent years. Accumulating evidence indicates that irisin has beneficial effects in the treatment of various diseases such as metabolic, cardiovascular and neurological disorders, especially bone-related diseases. Recent studies had shown that irisin plays the role in various bone diseases such as osteoarthritis, osteoporosis and other bone diseases, suggesting that irisin may be a potential molecule for the prevention and treatment of bone diseases. Therefore, in this review, by consulting the related domestic and international literature of irisin and bone diseases, we summarized the specific regulatory mechanisms of irisin in various bone diseases, and provided a systematic theoretical basis for its application in the diagnosis and treatment of the bone diseases.
Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study
Authors: Wang Meiti , Jin Guixiang , Cheng Ying , Guan Shi-Yang , Zheng Jinxin , Zhang Shun-Xian
Published: August 2023

Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis.

Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods.

Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) −18, IL-1β, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines.

Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.
Influenza breakthrough infection in vaccinated mice is characterized by non-pathological lung eosinophilia
Authors: Chang Lauren A. , Choi Angela , Rathnasinghe Raveen , Warang Prajakta , Noureddine Moataz , Jangra Sonia , Chen Yong , De Geest Bruno G. , Schotsaert Michael
Published: August 2023

Eosinophils are important mediators of mucosal tissue homeostasis, anti-helminth responses, and allergy. Lung eosinophilia has previously been linked to aberrant Type 2-skewed T cell responses to respiratory viral infection and may also be a consequence of vaccine-associated enhanced respiratory disease (VAERD), particularly in the case of respiratory syncytial virus (RSV) and the formalin-inactivated RSV vaccine. We previously reported a dose-dependent recruitment of eosinophils to the lungs of mice vaccinated with alum-adjuvanted trivalent inactivated influenza vaccine (TIV) following a sublethal, vaccine-matched H1N1 (A/New Caledonia/20/1999; NC99) influenza challenge. Given the differential role of eosinophil subset on immune function, we conducted the investigations herein to phenotype the lung eosinophils observed in our model of influenza breakthrough infection. Here, we demonstrate that eosinophil influx into the lungs of vaccinated mice is adjuvant- and sex-independent, and only present after vaccine-matched sublethal influenza challenge but not in mock-challenged mice. Furthermore, vaccinated and challenged mice had a compositional shift towards more inflammatory eosinophils (iEos) compared to resident eosinophils (rEos), resembling the shift observed in ovalbumin (OVA)-sensitized allergic control mice, however without any evidence of enhanced morbidity or aberrant inflammation in lung cytokine/chemokine signatures. Furthermore, we saw a lung eosinophil influx in the context of a vaccine-mismatched challenge. Additional layers of heterogeneity in the eosinophil compartment were observed via unsupervised clustering analysis of flow cytometry data. Our collective findings are a starting point for more in-depth phenotypic and functional characterization of lung eosinophil subsets in the context of vaccine- and infection-induced immunity.
Machine learning in predicting T-score in the Oxford classification system of IgA nephropathy
Authors: Xu Lin-Lin , Zhang Di , Weng Hao-Yi , Wang Li-Zhong , Chen Ruo-Yan , Chen Gang , Shi Su-Fang , Liu Li-Jun , Zhong Xu-Hui , Hong Shen-Da , Duan Li-Xin , Lv Ji-Cheng , Zhou Xu-Jie , Zhang Hong
Published: August 2023

Background

Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy.

Methods

A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (Tpre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus Tbio), and clinical variables and Tpre (base model plus Tpre) were developed separately in 1,168 patients with regular follow-up to evaluate whether Tpre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using Tpre.

Results

The features selected by AUCRF for the Tpre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the Tpre was 0.82 (95% CI: 0.80–0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75–0.97). When the Tbio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75–0.97) to 0.92 (95% CI: 0.85–0.98); P = 0.03]. There was no difference in AUC between the base model plus Tpre and the base model plus Tbio [0.90 (95% CI: 0.82–0.99) vs. 0.92 (95% CI: 0.85–0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using Tpre was 0.93 (95% CI: 0.87–0.99) in the external validation set.

Conclusion

A pathology T-score prediction (Tpre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.
Protein arginine methyltransferase 1 is a therapeutic vulnerability in multiple myeloma
Authors: Nguyen Hong Phuong , Le Anh Quynh , Liu Enze , Cesarano Annamaria , DiMeo Francesco , Perna Fabiana , Kapur Reuben , Walker Brian A. , Tran Ngoc Tung
Published: August 2023

Multiple myeloma (MM) is a devastating plasma cell malignancy characterized by the expansion of aberrant monoclonal plasma cells in the bone marrow, leading to severe clinical manifestations and poor prognosis, particularly in relapsed/refractory cases. Identifying novel therapeutic targets is crucial to improve treatment outcomes in these patients. In this study, we investigated the role of the protein arginine methyltransferase 1 (PRMT1) in MM pathogenesis and explored its potential as a therapeutic target. We observed that PRMT1, responsible for most asymmetric di-methylation in cells, exhibited the highest expression among PRMT family members in MM cell lines and primary MM cells. Importantly, PRMT1 expression was significantly elevated in relapsed/refractory patients compared to newly diagnosed patients. High expression of PRMT1 expression was strongly associated with poor prognosis. We found that genetic or enzymatic inhibition of PRMT1 impaired MM cell growth, induced cell cycle arrest, and triggered cell death. Treatment with MS023, a potent PRMT type I inhibitor, demonstrated a robust inhibitory effect on the viability of primary cells isolated from newly diagnosed and proteasome inhibitor-relapsed/refractory patients in a dose-dependent manner. Suppression of PRMT1 downregulated genes related to cell division and upregulated genes associated with apoptosis pathway. We also found that genes related to immune response and lymphocyte activation were significantly upregulated in PRMT1-suppressed cells. Notably, the activation status of T cells was strikingly enhanced upon co-culturing with PRMT1-KO MM cells. In vivo studies using a xenograft model revealed that targeting PRMT1 by either CRISPR/Cas9-mediated knockout or MS023 treatment significantly attenuated MM tumor growth and prolonged the survival of tumor-bearing mice. Histological analysis further confirmed increased apoptotic cell death in MS023-treated tumors. Collectively, our findings establish PRMT1 as an indispensable and novel therapeutic vulnerability in MM. The elevated expression of PRMT1 in relapsed/refractory patients underscores its potential as a target for overcoming treatment resistance. Moreover, our results highlight the efficacy of MS023 as a promising therapeutic agent against MM, offering new avenues for therapeutic approaches in relapsed/refractory MM.
Machine learning-driven exploration of drug therapies for triple-negative breast cancer treatment
Authors: Kaushik Aman Chandra , Zhao Zhongming
Published: August 2023

Breast cancer is the second leading cause of cancer death in women among all cancer types. It is highly heterogeneous in nature, which means that the tumors have different morphologies and there is heterogeneity even among people who have the same type of tumor. Several staging and classifying systems have been developed due to the variability of different types of breast cancer. Due to high heterogeneity, personalized treatment has become a new strategy. Out of all breast cancer subtypes, triple-negative breast cancer (TNBC) comprises ∼10%–15%. TNBC refers to the subtype of breast cancer where cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptors (ERs, PRs, and HERs). Tumors in TNBC have a diverse set of genetic markers and prognostic indicators. We scanned the Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases for potential drugs using human breast cancer cell lines and drug sensitivity data. Three different machine-learning approaches were used to evaluate the prediction of six effective drugs against the TNBC cell lines. The top biomarkers were then shortlisted on the basis of their involvement in breast cancer and further subjected to testing for radion resistance using data from the Cleveland database. It was observed that Panobinostat, PLX4720, Lapatinib, Nilotinib, Selumetinib, and Tanespimycin were six effective drugs against the TNBC cell lines. We could identify potential derivates that may be used against approved drugs. Only one biomarker (SETD7) was sensitive to all six drugs on the shortlist, while two others (SRARP and YIPF5) were sensitive to both radiation and drugs. Furthermore, we did not find any radioresistance markers for the TNBC. The proposed biomarkers and drug sensitivity analysis will provide potential candidates for future clinical investigation.
Association between sedentary behavior and risk of cognitive decline or mild cognitive impairment among the elderly: a systematic review and meta-analysis
Authors: Cai Xiao-ye , Qian Guo-ping , Wang Feng , Zhang Ming-yang , Da Ying-juan , Liang Jing-hong
Published: August 2023

Background

Existing evidence on the association between sedentary behavior (SB) and cognitive function remains inconclusive. Therefore, this study investigated the association between SB and the risk of cognitive decline (CD) or mild cognitive impairment (MCI) in the elderly.

Methods

A comprehensive search was independently conducted by two researchers (XC and GQ) in seven electronic databases, including Medline (via PubMed), China Biology Medicine, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, and VIP database for Chinese technical periodicals, covering studies published from the inception of database to June 2023. Studies that investigated the relationship between SB and the risk of CD or MCI in the elderly were included. The quality of the literature was assessed using the Newcastle–Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) assessment tools. The combined effect size analysis, subgroup analysis, and publication bias assessment were performed using STATA 14.0.

Results

A total of 13 cross-sectional and 6 cohort studies involving 81,791 individuals were included, comprising 17 high-quality studies and 2 medium-quality studies. We found that SB was significantly associated with an increased risk of CD [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.47–1.94] or MCI (OR = 1.34, 95% CI: 1.14–1.56) among the elderly. Subgroup analysis stratified according to comorbidity, lifestyle, family structure, publication year, and region showed statistical differences between groups, and the consistency of the results revealed the sources of the heterogeneity.

Conclusion

This meta-analysis showed that SB is positively associated with the risk of CD or MCI in the elderly, providing a higher level of evidence for the promotion of healthy behaviors by clinicians and health policymakers. Due to the number and quality of the included articles, more high-quality longitudinal studies are needed to further confirm our findings.
Evaluating the effects of PeakATP® supplementation on visuomotor reaction time and cognitive function following high-intensity sprint exercise
Authors: Moon Jessica M. , Dufner Trevor J. , Wells Adam J.
Published: August 2023

The purpose of this study was to examine the effects of 14-days adenosine 5′-triphosphate (ATP) supplementation (PeakATP®) on reaction time (RT), multiple object tracking speed (MOT), mood and cognition. Twenty adults (22.3 ± 4.4 yrs., 169.9 ± 9.5 cm, 78.7 ± 14.6 kg) completed two experimental trials in a double-blind, counter-balanced, crossover design. Subjects were randomized to either PeakATP® (400 mg) or placebo (PLA) and supplemented for 14-days prior to each trial. During each trial, subjects completed a three-minute all-out test on a cycle ergometer (3MT), with measures of visuomotor RT [Dynavision D2 Proactive (Mode A) and Reactive (Mode B) tasks], MOT (Neurotracker), mood (Profile of Mood States Questionnaire; POMS) and cognition (Automated Neuropsychological Assessment Metrics; ANAM) occurring before (PRE), immediately post (IP) and 60 min post-3MT (60P). Subjects ingested an acute dose of the assigned supplement 30 min prior to completing PRE assessments for each trial. Trials were separated by a 14-day washout period. PeakATP® significantly attenuated declines in hits (p = 0.006, ηp2 = 0.235) and average RT (AvgRT, p = 0.006, ηp2 = 0.236) in Mode A, significantly improved AvgRT (p = 0.039, ηp2 = 0.174) in Mode B, and significantly reduced the total number of misses (p = 0.005, ηp2 = 0.343) in Mode B. No differences between treatments were noted for MOT, POMS or ANAM variables. In conclusion, these results indicate that PeakATP® maintains proactive RT and improves reactive RT following high-intensity sprint exercise suggesting that supplemental ATP may mitigate exercise induced cognitive dysfunction.
Otolaryngology-related symptoms of COVID-19 in children in the post-epidemic era: a cross-sectional web-based survey study
Authors: Chen Yong-chao , Wang Xin , Teng Yi-shu , Jia De-sheng , Li Lan , Pan Hong-guang
Published: August 2023

Purpose

China adjusted and optimized its prevention and control strategies in December 2022, and it entered a new era of the coronavirus epidemic. Here, we describe the general and otolaryngology-related symptoms of coronavirus disease 2019 (COVID-19) in children during the first pandemic in the post-epidemic era, focusing on the frequency and severity of smell and taste loss, as well as the recovery process and its influencing factors.

Patients and methods

From 2 January to 7 January 2023, we conducted a cross-sectional online questionnaire survey through Questionnaire Stars in order to collect relevant information about COVID-19 in children in Shenzhen.

Results

A total of 1,247 valid questionnaires were received, with an effective response rate of 78.72%. All of the diagnoses were confirmed by nucleic acid or antigen test for COVID-19. Among the subjects, the sex ratio of male to female was more inclined to male (1.35:1), and the age was 3–16 years, with an average of 10.13 ± 2.82 years old. The most common symptoms were cough (58.24%), stuffy nose (56.18%), headache (42.09%), fatigue (40.44%), and sore throat (31.63%). Approximately 6.43% of the children reported dysosmia, the mean time of the duration of dysosmia was 5.38 ± 2.92 days, and the mean score of the severity of the dysosmia as assessed by visual analogue scale (VAS) was 4.63 ± 2.29. Approximately 13.34% reported dysgeusia, the mean time of the duration of dysgeusia was 4.77 ± 3.98 days, and the mean score of the severity of the dysgeusia as assessed by VAS was 5.12 ± 2.29. Univariate and multivariate logistic regression analysis showed that the prevalence of taste and olfactory disorders increased with age, mainly in children with severe symptoms and older children.

Conclusion

In the post-epidemic era, due to weakening of the pathogenicity of the subvariant of Omicron, overall condition of children with COVID-19 was mild, incidence of olfactory and taste disorders was low, recovery was faster, and prognosis was better. In our study, cough, runny nose, and sore throat were the most common symptoms, and the prevalence of taste and olfactory disorders increased with age, mainly in older children with severe symptoms.
Advances in the study of acetaminophen-induced liver injury
Authors: Li Xinghui , Ni Jiaqi , Chen Li
Published: August 2023

Acetaminophen (APAP) overdose is a significant cause of drug-induced liver injury and acute liver failure. The diagnosis, screening, and management of APAP-induced liver injury (AILI) is challenging because of the complex mechanisms involved. Starting from the current studies on the mechanisms of AILI, this review focuses on novel findings in the field of diagnosis, screening, and management of AILI. It highlights the current issues that need to be addressed. This review is supposed to summarize the recent research progress and make recommendations for future research.
Reference standards for the 6-min walk test in Croatian older adults
Authors: Sagat Peter
Published: August 2023

Introduction: The 6-min walk test (6MWT) is commonly used to assess the level of functional capacity of individuals with respiratory diseases. Although previous evidence has provided reference standards for the 6MWT in unhealthy older adults, no data have been provided for the Croatian healthy older populations. Therefore, the main purposes of the study were to define sex- and age-specific references for the 6MWT in older adults.

Methods: Six-hundred and forty-three older adults (260 men and 383 women) aged 60–80 years were recruited in this observational cross-sectional study. The participants were instructed to walk the maximal distance possible for 6 min. The main outcome was the final score in the 6MWT conducted at a 30-m straight corridor.

Results: Men exhibited longer walking distance, compared to women (678.3 ± 59.1 vs. 653.8 ± 49.9 m, p < 0.001) and younger men and women performed better, than their older counterparts (p < 0.001). However, the sex*age interaction effect showed no significant differences between men and women in the same age range (p = 0.865).

Discussion: This is the first study with the purpose of providing reference standards for the 6MWT in a large sample of Croatian older adults. Older men and women in lower percentiles may be treated as a “risky group” of individuals with a special attention of implementing interventions to enhance the performance.
Healthcare resource use and costs reduction with aripiprazole once-monthly in schizophrenia: AMBITION, a real-world study
Authors: Sanchez-Gistau Vanessa , Moreno María José , Gómez-Lus Susana , Sicras-Mainar Antoni , Crespo-Facorro Benedicto
Published: August 2023

Objective

This study aims to compare the hospitalization rate in individuals with schizophrenia who started their treatment with aripiprazole once monthly (AOM400) or atypical oral antipsychotics (OA) in Spain.

Methods

This is an observational and retrospective study based on the electronic medical records from the BIG-PAC database. The study population consisted of individuals diagnosed with schizophrenia who initiated their treatment with AOM400 (AOM cohort) or atypical OA (OA cohort) from 01/01/2017 to 31/12/2019. A 1:1 propensity score matching (PSM) procedure was conducted to match individuals of both cohorts. The number and duration of hospitalizations, persistence to treatment, healthcare resources use, and costs were analyzed after 12 months.

Results

After the PSM, 1,017 individuals were included in each cohort [age: 41.4 years (SD: 10.6); males: 54.6%]. During the follow-up period, the AOM cohort had a 40% lower risk of hospitalization than the OA group [HR: 0.60 (95% confidence interval, CI: 0.49–0.74)]. The median time to the first hospitalization was longer in individuals with AOM400 compared to those with OA (197 days compared to 174 days; p < 0.004), whereas hospital admissions were shorter (AOM400: 6 compared to OA: 11 days; p < 0.001). After 12 months, individuals receiving AOM400 were more persistent than those with OA (64.9% compared to 53.7%; p < 0.001). The OA cohort required more healthcare resources, mainly visits to primary care physicians, specialists, and emergency rooms than those receiving AOM400 (p ≤ 0.005 in all comparisons). AOM400 reduced the costs of hospitalizations, and emergency room, specialist and primary care visits by 50.4, 36.7, 16.1, and 10.9%, respectively, in comparison to the treatment with atypical OA. AOM400 led to annual cost savings of €1,717.9 per individual, from the societal perspective.

Conclusion

Aripiprazole once monthly reduces the number and duration of hospitalizations, together with the treatment costs of schizophrenia, as it reduces the use of healthcare resources and productivity losses in these individuals.
Slouching towards engagement: interactions between people using psychedelics naturalistically and their healthcare providers
Authors: Boehnke Kevin F. , Cox Kasey , Weston Cody , Herberholz Moss , Glynos Nicolas , Kolbman Nicholas , Fields Christopher W. , Barron Julie , Kruger Daniel J.
Published: August 2023

Introduction

There is substantial public interest in psychedelics as potential treatments for psychiatric conditions. However, most psychedelics are criminalized under federal law in the USA, so it is unclear whether use occurs with clinical support. Our objective was to assess whether naturalistic psychedelic use occurs with clinical support, interactions between those using psychedelics and healthcare providers (psychiatrist, therapist, or primary physicians), and use characteristics.

Methods

We conducted an online, anonymous, confidential, cross-sectional survey of adults reporting psychedelic use (N = 1221) through a psychedelics advocacy event and social media between 9/18/2022 and 11/5/2022. We assessed participant disclosure of psychedelic use with their psychiatric care provider (PsyCP) and/or primary care provider (PCP), desire for provider support, access to support, and rate of taking prescribed psychoactive medications alongside psychedelics.

Results

Among participants with such care providers, 22% disclosed psychedelic use to their PCP vs. 58% to their PsyCP. Participants were less confident in PCP vs. PsyCP ability to integrate psychedelics into treatment. Common reasons for nondisclosure included stigma, inadequate provider knowledge, and legal concerns. 23% reported taking psychedelics on the same day as potentially interacting psychiatric medications (e.g., anxiolytics, antidepressants). Despite 81% of participants desiring therapist support during psychedelic experiences, only 15% had received such support.

Discussion

Our results show that psychedelic use is generally disconnected from primary and psychiatric clinical care. This disconnection may result in safety issues, including inadequate screening for contraindicated conditions, lack of support during emergent adverse events, and drug interactions. Enhanced clinical education and orienting drug policy towards known harms and benefits of psychedelics is needed.
Reframing human trafficking awareness campaigns in the United States: goals, audience, and content
Authors: Savoia Elena , Piltch-Loeb Rachael , Muibu Daisy , Leffler Amy , Hughes Diana , Montrond Alberto
Published: August 2023

Introduction

Human trafficking (HT) awareness campaigns can educate the public and specific professional figures about this crime and ways to prevent it. However, there currently remains a gap in terms of how to best frame such campaigns without stigmatizing groups of individuals or portraying victims in unrealistic ways.

Methods

We conducted four focus groups with 22 experts in HT to explore their perspectives and opinions on current challenges in the framing of HT awareness campaigns in the United States. Focus groups were conducted via Zoom and transcribed verbatim. Two independent reviewers analyzed the transcripts to identify themes using an inductive approach. The results of the focus groups analysis were used to structure the guiding questions of a brainstorming technique named Nominal Group Technique (NGT). Fifteen of 22 experts that participated in the focus groups joined the in-person NGT with the intent of generating ideas and achieving consensus on target audiences, goals, and content of human trafficking awareness campaigns. At the end of the NGT participants ranked priority for actions in the development of HT awareness efforts in the United States.

Results

During the NGT the experts provided a number of recommendations to improve HT awareness and to empower victims to reach for help. They pointed to the need for: awareness efforts that describe HT on a spectrum of human abuse and exploitation; training for professional figures about trauma-informed care and communication; and efforts that empower trafficked victims to seek support. They also pointed to the need to develop awareness efforts tailored to local needs in close collaborations with the community-based organizations that can champion their dissemination and be the primary point of access for victims seeking help.