bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for
Attention-deficit Hyperactivity Disorder
Authors: Shirooie Samira , Noori Tayebeh , Sahebgharani Mousa , Sureda Antoni , Sobarzo-Sanchez Eduardo , Fakhri Sajad 
Published: January 2022

Abstract:
Attention-Deficit Hyperactivity Disorder (ADHD) is a highly prevalent childhood psychiatric
disorder. In general, a child with ADHD has significant attention problems with difficulty
concentrating on a subject and is generally associated with impulsivity and excessive activity. The
etiology of ADHD in most patients is unknown, although it is considered to be a multifactorial disease
caused by a combination of genetics and environmental factors. Diverse factors, such as the existence
of mental, nutritional, or general health problems during childhood, as well as smoking and
alcohol drinking during pregnancy, are related to an increased risk of ADHD. Behavioral and psychological
characteristics of ADHD include anxiety, mood disorders, behavioral disorders, language
disorders, and learning disabilities. These symptoms affect individuals, families, and communities,
negatively altering educational and social results, strained parent-child relationships, and increased
use of health services. ADHD may be associated with deficits in inhibitory frontostriatal noradrenergic
neurons on lower striatal structures that are predominantly driven by dopaminergic neurons.
Phosphoinositide 3-kinases (PI3Ks) are a conserved family of lipid kinases that control a number of
cellular processes, including cell proliferation, differentiation, migration, insulin metabolism, and
apoptosis. Since PI3K plays an important role in controlling the noradrenergic neuron, it opens up
new insights into research on ADHD and other developmental brain diseases. This review presents
evidence for the potential usefulness of PI3K and its modulators as a potential treatment for ADHD.
Ligand-based Modeling of CXC Chemokine Receptor 4 and Identification
of Inhibitors of Novel Chemotypes as Potential Leads towards New Anti-
COVID-19 Treatments
Authors: Daoud Safa , Taha Mutasem 
Published: January 2022

Background:
Chemokines are involved in several human diseases and different stages of
COVID-19 infection. They play a critical role in the pathophysiology of the associated acute respiratory
disease syndrome, a major complication leading to death among COVID-19 patients. In particular,
CXC chemokine receptor 4 (CXCR4) was found to be highly expressed in COVID-19 patients.

Methods:
We herein describe a computational workflow based on combining pharmacophore modeling
and QSAR analysis towards the discovery of novel CXCR4 inhibitors. Subsequent virtual screening
identified two promising CXCR4 inhibitors from the National Cancer Institute (NCI) list of compounds.
The most active hit showed in vitro IC50 value of 24.4 μM.

Results and Conclusion:
These results proved the validity of the QSAR model and associated pharmacophore
models as means to screen virtual databases for new CXCR4 inhibitors as leads for the
development of new COVID-19 therapies.
Anti-inflammatory Effect of Predimenol, A Bioactive Extract from Phaleria
macrocarpa, through the Suppression of NF-κB and COX-2
Authors: Yuliana Yurike , Tandrasasmita Olivia M. , Tjandrawinata Raymond R. 
Published: January 2022

Background:
Inflammation is the response to the reaction of any type of bodily injury
by elevating cellular metabolism and releasing soluble mediators. It is also a contributing factor of
pain. Predimenol, which has previously been known as DLBS1442, is a bioactive extract from Phaleria
macrocarpa (Scheff.) Boerl (Thymelaceae). It can be an alternative treatment for pain relief,
especially for long-term use.

Objective:
The objective of this study is to evaluate the anti-inflammatory activities of predimenol
through the evaluation of several parameters involved in the inflammatory pathway.

Methods:
Cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-
α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), and nuclear factor
κB (NF-κB) were observed after 24 h exposure of predimenol (0-180 μg/mL) to
lipopolysaccharides (LPS)-activated RAW 264.7 cell. The inflammatory markers were measured
using nitric oxide (NO) assay and enzyme-linked immunosorbent assay (ELISA) for COX-2 inhibitor
assay. The gene expressions of TNF-α, IL-1β, IL-2 and IL-6 were quantified using the polymerase
chain reaction (PCR) method. Western blotting was applied to detect phosphorylated IκB
kinase (IKK) protein to confirm the activation of NF-κB.

Results:
Our study showed a similar mechanism with most non-steroidal anti-inflammatory drugs
(NSAIDs). Predimenol consistently downregulated the expression of iNOS and inhibited COX-2
activity. Moreover, predimenol significantly inhibited the LPS-induced production of NO, TNF-α,
IL-1β, IL-2 and IL-6. Down-regulation of these markers was suggested due to the reduction of NF-
κB transcription level and activation by predimenol.

Conclusion:
Predimenol exhibits anti-inflammatory activities through NF-kB inactivation-mediated
COX-2 suppression, which may suggest that predimenol is a potential analgesic and anti-inflammatory
agent.
Candidemia Risk Prediction (CanDETEC) Model for Patients With Malignancy: Model Development and Validation in a Single-Center Retrospective Study
Authors: Yoo Junsang , Kim Si-Ho , Hur Sujeong , Ha Juhyung , Huh Kyungmin , Cha Won Chul 
Published: January 2022

Background
Appropriate empirical treatment for candidemia is associated with reduced mortality; however, the timely diagnosis of candidemia in patients with sepsis remains poor.

Objective
We aimed to use machine learning algorithms to develop and validate a candidemia prediction model for patients with cancer.

Methods
We conducted a single-center retrospective study using the cancer registry of a tertiary academic hospital. Adult patients diagnosed with malignancies between January 2010 and December 2018 were included. Our study outcome was the prediction of candidemia events. A stratified undersampling method was used to extract control data for algorithm learning. Multiple models were developed—a combination of 4 variable groups and 5 algorithms (auto-machine learning, deep neural network, gradient boosting, logistic regression, and random forest). The model with the largest area under the receiver operating characteristic curve (AUROC) was selected as the Candida detection (CanDETEC) model after comparing its performance indexes with those of the Candida Score Model.

Results
From a total of 273,380 blood cultures from 186,404 registered patients with cancer, we extracted 501 records of candidemia events and 2000 records as control data. Performance among the different models varied (AUROC 0.771- 0.889), with all models demonstrating superior performance to that of the Candida Score (AUROC 0.677). The random forest model performed the best (AUROC 0.889, 95% CI 0.888-0.889); therefore, it was selected as the CanDETEC model.

Conclusions
The CanDETEC model predicted candidemia in patients with cancer with high discriminative power. This algorithm could be used for the timely diagnosis and appropriate empirical treatment of candidemia.
The Challenges in Designing a Prevention Chatbot for Eating Disorders: Observational Study
Authors: Chan William W , Fitzsimmons-Craft Ellen E , Smith Arielle C , Firebaugh Marie-Laure , Fowler Lauren A , DePietro Bianca , Topooco Naira , Wilfley Denise E , Taylor C Barr , Jacobson Nicholas C 
Published: January 2022

Background
Chatbots have the potential to provide cost-effective mental health prevention programs at scale and increase interactivity, ease of use, and accessibility of intervention programs.

Objective
The development of chatbot prevention for eating disorders (EDs) is still in its infancy. Our aim is to present examples of and solutions to challenges in designing and refining a rule-based prevention chatbot program for EDs, targeted at adult women at risk for developing an ED.

Methods
Participants were 2409 individuals who at least began to use an EDs prevention chatbot in response to social media advertising. Over 6 months, the research team reviewed up to 52,129 comments from these users to identify inappropriate responses that negatively impacted users’ experience and technical glitches. Problems identified by reviewers were then presented to the entire research team, who then generated possible solutions and implemented new responses.

Results
The most common problem with the chatbot was a general limitation in understanding and responding appropriately to unanticipated user responses. We developed several workarounds to limit these problems while retaining some interactivity.

Conclusions
Rule-based chatbots have the potential to reach large populations at low cost but are limited in understanding and responding appropriately to unanticipated user responses. They can be most effective in providing information and simple conversations. Workarounds can reduce conversation errors.
Прогнозування ефективності терапії алкогольного цирозу печінки
Authors: Samogalska O.Ye. , Lazarchuk T.B. , Babyak O.V. , Vitruk I.M. 
Published: January 2022

Для створення прогностичної таблиці ефективності терапії алкогольного цирозу печінки проаналізували 21 показник лабораторних досліджень. Для прогнозування ефективності терапії використовували інтегральну оцінку — сума балів по 15 прогностичних показниках. Сума балів, що перевищувала +13, свідчить про високу ймовірність успішності стандартної терапії. При сумі балів менше –13 імовірність неуспіху становить 95 %. Якщо сума балів перебуває в проміжку від +13 до –13, то інформації недостатньо для ухвалення конкретного рішення. Визначення високого ризику неефективності стандартної терапії допускає розробку індивідуальної програми лікування хворих на алкогольний цироз печінки з розрахуванням індексу маси тіла.
Функціональний стан шлунка та імунологічна резистентність у дітей перших місяців життя
Authors: Dmytriieva S.M. 
Published: January 2022

У статті подано результати дослідження функціонального стану шлунка, показників неспецифічної резистентності та мікробної колонізації кишечника в новонароджених та дітей перших місяців життя. Встановлено, що в перші місяці життя віковою особливістю є слабокислий інтрагастральний рН (4,6 ± 0,5). Цикл міжтравної моторики визначається режимом годування малюків. При повній евакуації шлункового вмісту через 2,5–3,0 години після годування дитини моторика шлункових скорочень становить (5,4 ± 0,4), внутрішньошлунковий тиск — (13,1 ± 1,3) мм рт.ст. Показано, що функціональне становлення шлунково-кишкового тракту здійснюється у взаємозв’язку з процесами формування місцевих факторів неспецифічного захисту травної системи та фізіологічної контамінації кишечника.
Стеатоз печени и стеатогепатит — неизбежность смешанного генеза
Authors: Stepanov Yu.M. 
Published: January 2022

Представлен анализ этиологических и патогенетических механизмов формирования стеатоза и стеатогепатита смешанного генеза. Показано, что одним из основных этиопатогенетических факторов развития стеатоза печени и стеатогепатита остается алкоголь, роль которого прослеживается у 46–65 % пациентов. Накоплены убедительные данные, свидетельствующие о том, что ожирение, инсулинорезистентность представляют собой факторы прогрессирования стеатоза и стеатогепатита алкогольной, неалкогольной и смешанной этиологии. Одновременное влияние нескольких этиологических факторов приводит к незамедлительному развитию стеатоза и стеатогепатита у 95 % пациентов. Многие триггерные факторы можно рассматривать как взаимодополняющие факторы поражения печени смешанного генеза. Приведены общие подходы к диагностике, лечению, представлены основные группы лекарственных препаратов для коррекции стеатоза и стеатогепатита смешанного генеза.
Landslide Risk Analysis in Kelud Volcano, East Java, Indonesia
Authors: Bachri Syamsul , Sumarmi Sumarmi , Utaya Sugeng , Irawan Listyo Yudha , Wahyu Ning Tyas Lela , Dwitri Nurdiansyah Farizki , Erfika Nurjanah Alif , Wirawan Rahmat , Amri adillah Akhmad , Setia Purnama Denny 
Published: January 2022

Pandansari village became one of the villages that has frequent landslide events in the period 2009-2015 compared with the surrounding area in Malang regency. The purpose of this study was to determine the level of landslide risk located within an active volcano. To enhance the comprehensive analysis of landslide disasters, we used a risk concept in this study. The landslide risk analysis was based on 3 determinants, namely hazards, community vulnerability, and regional capacity. The data collections were conducted using observation and documentation for landslide hazards and interviews as well as Focus Group Discussion (FGD) for vulnerability and capacity aspects. The interviewed were applied for community and local government of Pandansari village. The recorded interviews were transcribed and analyzed according to recurrent themes in the answers. Findings from field investigation were then confronted with previous existing concepts of human exposure to natural hazards. Furthermore, the landslide hazard data were analyzed using spatial analysis tools, including GIS scoring, weighting, and overlaying weighted sum. The results showed the level of landslide risk has different values depending on the risk parameter, community vulnerability, and regional capacity. The level of landslide risk was divided into three levels, namely high with an area of 557.71 ha, moderate with 774.49 ha, and low with 1118.77 ha. Each of the risk factors, vulnerability, and capacity, has its characteristics in influencing the landslide risk in Pandansari Village. In relation to landslide disaster management, the risk analysis gives comprehensive input reaching good management practice in Pandansari village.
Unregistered artesian Well Management in Pasuruan, Indonesia: An Attempt to Protect Groundwater Resources
Authors: Hendrayana Heru , Riyanto Indra Agus , Nuha Azmin , Lisan Ahmad Rif’an Khoirul 
Published: January 2022

The number of unregistered artesian wells increases every year in the northern slopes of Bromo Volcano, Pasuruan. Artesian wells are used for domestic needs and agricultural irrigation but are not followed by environmentally sound groundwater use. The purpose of this study is to assess the potential for groundwater, groundwater use, wasted groundwater, and recommendations for groundwater management. The groundwater potential was obtained by measuring the depth of the groundwater table, piezometric surface of artesian wells, and geoelectrical data. Water uses were obtained from calculations based on the Indonesian National Standard. The amount of wasted groundwater was obtained by comparing the groundwater potentials, groundwater uses, and groundwater discharges from unregistered artesian wells. Water transfer was assessed by selecting unregistered artesian wells with discharges able to fulfill the water demands of each village. Groundwater in the Sub-Districts of Gondang Wetan and Winongan has high potential consisting of 1 unconfined aquifer group and two confined aquifer groups. Gondang Wetan and Winongan Sub-Districts are characterized as wasting groundwater potential through unregistered artesian wells. The discharge flow of unregistered artesian wells exceeds the water needs (>100%) in Winongan and Gondang Wetan Sub-Districts. Groundwater can be managed by water transfer, closure of artesian wells, and regulation of artesian wells use. Water can be transferred to areas not covered by Artesian wells in 20 villages. The number of artesian wells used for water transfer is 20 with a discharge of 5-20 liters/s.
PERTUMBUHAN MEGAURBAN KEDUNGSEPUR
Authors: Wilonoyudho Saratri 
Published: January 2022

Over the last 20 years many urban areas have experienced dramatic growth, as a result of rapid population increase and the trans formation of the world economy because of a combination of rapid technological and political change. In the case of Kedungsepur, the area has seen more than twofold growth. Migrants come to the inner zones from both the area's core and elsewhere in the country. Net migration, in many case, contributes as much as two thirds of the population growth in these zones, whereas in the city cores, net migration contributes little to growth. A comprehensive model suggests that urbanization in Kedungsepur is influenced by structural and social demographic factors. Thus, the balance between managing urban discharges to the environment and enhancing environmental resource capacity is the key determinant of sustainability.
ANALYSIS OF FACTORS AFFECTING THE USE OF CASHLESS MOBILE PAYMENT IN MILLENIAL GENERATIONS OF BATAM CITY
Authors: Suprapto Yandi 
Published: January 2022

The purpose of this study is to determine the factors or influences that lead to the use of cashless mobile payments on the Batam millennial generation. The number of electronic-based payment media provided is expected to be able to create payment transactions that are practical, efficient, safe and encourage the creation of a Less Cash Society (LCS). When compared to Indonesia with other ASEAN countries, the level of use of electronic-based payments in the community is still low. Generation Y or the Millennial generation (15 to 39 years) in 2017 showed a figure of 40.29% or as many as 105,520,300 individuals from 261,890,900 Indonesians considered to have the potential to increase the use of electronic-based payments and encourage public awareness of LCS.
The intention to use cashless mobile payments is the dependent variable. Attitudes, behavioral beliefs, financial costs, security and social influence act as independent variables for this study. Determination of the research object was carried out by purposive sampling method, namely the millennial generation (15 to 39 years) in Batam. Research data collection is based on the questionnaire method, namely electronic and online questionnaires with 230 collected data. The research data were analyzed through multiple regression analysis using SSPSS.
The results obtained indicate that the variables of attitude, security and social influence have a significant positive effect on the intention to use cashless mobile payment, while the variables of behavioral beliefs and financial costs do not have a significant effect on the intention to use cashless mobile payments.
The Impact of the Stress Hyperglycemia Ratio on Short-term and Long-term Poor Prognosis in Patients With Acute Coronary Syndrome: Insight From a Large Cohort Study in Asia
Authors: Yang Jie , Zheng Yitian , Li Chen , Gao Jun , Meng Xiangbin , Zhang Kuo , Wang Wenyao , Shao Chunli , Tang Yi-Da 
Published: January 2022

OBJECTIVE
In recent years, some studies have indicated that a novel marker described as the stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with the short-term poor prognosis in patients with acute myocardial infarction. In the current study we evaluated the association of SHR with adverse cardiovascular events among patients with acute coronary syndrome (ACS).

RESEARCH DESIGN AND METHODS
We consecutively enrolled 5,562 ACS patients who underwent drug-eluting stent (DES) implantation. All subjects were divided into five groups according to SHR, which was determined by the following formula: ABG / [(28.7 × HbA1c %) − 46.7], where ABG is admission blood glucose level. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE) at the 2-year follow-up, and the secondary end point included major adverse cardiovascular events (MACE) at 2-year follow-up, cardiac death, and nonfatal myocardial infarction (MI) at 2-year follow-up and in-hospital cardiac death and nonfatal MI.

RESULTS
A total of 643 MACCE were recorded during a median follow-up of 28.3 months. Kaplan-Meier survival analysis showed the lowest MACCE incidence in quintile 3 (P &lt; 0.001). Moreover, the outcomes of restricted cubic spline analysis suggested that there was a U-shaped or J-shaped association between the SHR and early and late cardiovascular outcomes even after adjustment for other confounding factors.

CONCLUSIONS
There were U-shaped associations of SHR with MACCE rate and MACE rate at 2-year follow-ups and J-shaped associations of SHR with in-hospital cardiac death and MI and that at 2-year follow-up in ACS patients who underwent DES implantation, and the inflection point of SHR for poor prognosis was 0.78.
The Gut Microbiome of Adults With Type 1 Diabetes and Its Association With the Host Glycemic Control
Authors: Shilo Smadar , Godneva Anastasia , Rachmiel Marianna , Korem Tal , Bussi Yuval , Kolobkov Dmitry , Karady Tal , Bar Noam , Wolf Bat Chen , Glantz-Gashai Yitav , Cohen Michal , Levin Nehama Zuckerman , Shehadeh Naim , Gruber Noah , Levran Neriya , Koren Shlomit , Weinberger Adina , Pinhas-Hamiel Orit , Segal Eran 
Published: January 2022

OBJECTIVE
Previous studies have demonstrated an association between gut microbiota composition and type 1 diabetes (T1D) pathogenesis. However, little is known about the composition and function of the gut microbiome in adults with longstanding T1D or its association with host glycemic control.

RESEARCH DESIGN AND METHODS
We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 74 adults with T1D, 14.6 ± 9.6 years following diagnosis, and compared their microbial composition and function to 296 age-matched healthy control subjects (1:4 ratio). We further analyzed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measurements and blood tests and constructed a prediction model that solely takes microbiome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from control subjects.

RESULTS
Adults with T1D had a distinct microbial signature that separated them from control subjects when using prediction algorithms on held-out subjects (area under the receiver operating characteristic curve = 0.89 ± 0.03). Linear discriminant analysis showed several bacterial species with significantly higher scores in T1D, including Prevotella copri and Eubacterium siraeum, and species with higher scores in control subjects, including Firmicutes bacterium and Faecalibacterium prausnitzii (P &lt; 0.05, false discovery rate corrected for all). On the functional level, several metabolic pathways were significantly lower in adults with T1D. Several bacterial taxa and metabolic pathways were associated with the host’s glycemic control.

CONCLUSIONS
We identified a distinct gut microbial signature in adults with longstanding T1D and associations between microbial taxa, metabolic pathways, and glycemic control indices. Additional mechanistic studies are needed to identify the role of these bacteria for potential therapeutic strategies.