bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug shortages in Israel, revisited: a bitter pill to swallow
Authors: Schwartzberg Eyal , Marom Eli , Vishkautzan Alla , Gorelik Einat , Shani Segev 
Published: March 2024

Abstract
Background
In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue.

Methods
We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and their reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed.

Results
Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined.

Conclusion
Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.
Catalysing global surgery: a meta-research study on factors affecting surgical research collaborations with Africa
Authors: Kirengo Thomas O. , Dossajee Hussein , Onyango Evans M. , Rachakonda Reema H. , Schneider Bailey , Sela Declan P. , Hosseinzadeh Zahra , Nadeem Zohaib , Obonyo Nchafatso G. 
Published: March 2024

Abstract
Introduction
In December 2019, the COVID-19 pandemic highlighted the urgent need for rapid collaboration, research, and interventions. International research collaborations foster more significant responses to rapid global changes by enabling international, multicentre research, decreasing biases, and increasing study validity while reducing overall research time and costs. However, there has been low uptake of collaborative research by African institutions and individuals.

Aim
To systematically review facilitating factors and challenges to collaborative surgical research studies conducted in Africa.

Methodology
A meta-research review using PubMed®/MEDLINE and Embase on surgical collaboration in Africa from 1st of January 2011 to 31st of September 2021 in accordance to PRISMA guidelines. Surgical studies by collaborative groups involving African authors and sites were included (55 papers). Data on the study period, geographical regions, and research scope, facilitating factors, and challenges were extracted from the studies retrieved from the search.

Results
Most of the collaborations in Africa occurred with European institutions (76%). Of the 54 African countries, 63% (34/54) participated in surgical collaborations. The highest collaboration frequency occurred in South Africa (11%) and Nigeria (8%). However, most publications originated from Eastern Africa (43%). Leveraging synergies between high- and low- to middle-income countries (LMICs), well-defined structures, and secure data platforms facilitated collaboration. However, the underrepresentation of collaborators from LMICs was a significant challenge.

Conclusion
Available literature provides critical insights into the facilitating factors and challenges of research collaboration with Africa. However, there is a need for a detailed prospective study to explore the themes highlighted further.

Systematic review registration
PROSPERO 2022 CRD42022352115.
Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: study design and methodological considerations
Authors: McLeman Bethany , Gauthier Phoebe , Lester Laurie S. , Homsted Felicity , Gardner Vernon , Moore Sarah K. , Joudrey Paul J. , Saldana Lisa , Cochran Gerald , Harris Jacklyn P. , Hefner Kathryn , Chongsi Edward , Kramer Kimberly , Vena Ashley , Ottesen Rebecca A. , Gallant Tess , Boggis Jesse S. , Rao Deepika , Page Marjorie , Cox Nicholas , Iandiorio Michelle , Ambaah Ekow , Ghitza Udi , Fiellin David A. , Marsch Lisa A. 
Published: March 2024

Abstract
Background
Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care.

Methods
This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site’s capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber).

Discussion
This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients’ access to MOUD and treatment outcomes.
Trial registration: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www.clinicaltrials.gov/study/NCT05310786?id=NCT05310786&rank=1
New development of compact magnetic separator for on-site material screening in various geological survey
Authors: Jinnouchi So , Uyeda Chiaki , Hisayoshi Keiji , Takayama Gen , Terada Kentaro 
Published: March 2024

AbstractMagnetic separation has been recognized as a valuable technique for extracting or separating target materials from mixed heterogeneous particles. In conventional geological research, it has been used to separate ferro- and ferri-magnetic minerals such as Fe–Ni metal, magnetite and ilmenite. Recently, a mixture of diamagnetic and weak paramagnetic particles has been successfully separated into groups of different materials using a compact magnetic circuit; however, the resolution was not sufficiently high to analyze various heterogeneous particles studied in geological research. Here, we show that the resolution has remarkably improved by developing new magnetic separator. Accordingly, the separation efficiency of particles due to magnetic translation increased by a factor of ~ 2.5, and two different materials were definitely resolved when their variance of the magnetic susceptibility exceeded ~ 2 × 10−7 emu/g; previously, limit of the resolution was above 7 × 10–7 emu/g. We also established the orbit simulation program in magnetic and gravitational field, which accurately predicted the actual trajectory due to magnetic translation. The improved separation resolution of the new separator has significantly increased the range of solid materials that can be magnetically separated, and the range of applications has been considerably expanded to include the matrix of primitive meteorites, surface soils of solid planets and satellites, volcanic ash and sedimentary rocks. The newly developed device is compact and requires little electric power, allowing on-site material screening in various geological research.
Temporary slip speed increases during short-term slow slip events with durations of one to three hours
Authors: Katsumata Akio , Miyaoka Kazuki , Tsuyuki Takahiro , Itaba Satoshi , Tanaka Masayuki , Ito Takeo , Takamori Akiteru , Araya Akito 
Published: March 2024

AbstractTemporary slip speed increases with durations of 1–3 h were identified during short-term slow slip events in records of borehole and laser strainmeters in the Tokai region, Japan. They were found by searching for peaks of correlation coefficients between stacked strain data and ramp functions with rise times of 1 and 2 h. Although many of the strain steps were considered due to noise, some strain steps occurred with simultaneous activation of the deep tectonic tremors and shared source areas with the tremors. From 2016 to 2022, we observed five strain steps with simultaneous activation of tectonic tremors and coincidence of source locations with the tremors. Those strain steps occurred during short-term slow slip events and were temporary slip speed increases of the slow slip events. Those strain steps seemed to be related to successive occurrences with source migration of short-term slow slip events. The detrended strain steps corresponded to plate boundary slip events of moment magnitude around 5, which was consistent with the scaling law of slow earthquakes.
Graphical Abstract
Association of food consumption patterns and nutritional status of children under 5 years from rural households in Northern regions, Namibia
Authors: Angula Maria , Ishola Anthony , Tjiurutue Muvari , Chigonga Nozizwe , Sulyok Michael , Krska Rudolf , Ezekiel Chibundu N. , Misihairabgwi Jane 
Published: March 2024

Abstract
Background
Many developing countries, Namibia included, have a high prevalence of malnutrition among children, especially in rural subsistence farming areas where inadequate food supply is common. Poor diets in children under 5 years may result in negative health impacts. This study determined the association of food consumption patterns and nutritional status of children under 5 years from rural households in Oshana and Oshikoto regions in Namibia.

Method
Employing a cross-sectional descriptive design, 377 children under 5 years participated in this study using purposive sampling. Validated dietary diversity and food frequency questionnaires were used to obtain information on demographic characteristics, commonly consumed food per week, and meal frequencies for the recruited children. Anthropometric measurements were obtained to assess nutritional status of children using Emergency Nutrition Assessment (ENA) software. Descriptive and inferential statistics were computed using the IBM® SPSS® Statistics (Statistical Package for Social Sciences) version 27.

Results
Staple foods, mostly grains, roots and tubers, along with flesh foods, legumes and nuts were commonly consumed. Vitamin A-rich fruits and vegetables were solely consumed in Oshana region (10.7%) and not in Oshikoto. Oshana exhibited a lower dietary diversity score (4±1 SD) compared to Oshikoto (5±1 SD). The prevalence of adequate feeding practices varied, with Oshana having 38.8% meeting minimum milk feeding frequency (MMFF), 55.6% minimum dietary diversity (MDD), 69.8% minimum meal frequency (MMF), and 27% minimum acceptable diet (MAD). In Oshikoto, these figures were lower at 2%, 7%, 32%, and 0.5%, respectively. Stunting, underweight, wasting, and overweight were also documented, with slight differences between the two regions. The study did not find association between nutritional status and MMFF, MDD and MAD. However, significant associations were found between specific food types, amount of food, breastfeeding length, MMF and malnutrition indicators in both regions (p<0.05).

Conclusion
Most study participants consumed locally available staple foods. Stunting, underweight, and wasting were prevalent among children in the two regions which were significantly associated to the amount of food consumed, MMF and/ some food types. Improving food environments and eliminating access barriers to diversified diets can mitigate high prevalence of malnutrition among rural children.
A narrative review of the therapeutic and remedial prospects of cannabidiol with emphasis on neurological and neuropsychiatric disorders
Authors: Omotayo Oluwadara Pelumi , Lemmer Yolandy , Mason Shayne 
Published: March 2024

Abstract
Background
The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed.

Main body
This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion.

Conclusion
CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD’s therapeutic tendencies in neurological/neuropsychiatric disorders.
Frequency of burnout in dental students and its relationship with stress level, depressive, and anxiety state
Authors: Alhilali Khetam , Husni Mariwan , Almarabheh Amer 
Published: March 2024

Abstract
Background
This study aimed to identify the prevalence of burnout in dental students at the Dentistry School of University of Qadisiya, Iraq. All students at the dentistry school were invited to participate in the study. Medical and dental education is a highly demanding endeavor. Burnout is associated with anxiety, depression, and stress levels. Addressing these psychological factors and manage them early will improve the well-being of students.

Material and methods
A cross-sectional questionnaire survey was conducted with the participation of 147 dentistry school students. The students completed a sociodemographic data form, the Depression Anxiety Stress Scale-21 (DASS-21), and the Maslach Burnout Inventory (MBI).

Results
The DASS-21 scale scores for all three components (depression, anxiety, and stress) were high in 74.1%, 90.4%, and 98% of the respondents, respectively. The results also showed that high scores of emotional exhaustion, depersonalization, and personal accomplishment were reported in 50.3%, 67.3%, and 89.8% respectively. MBI revealed a significant association with presence of an established diagnosis of a mental illness or a chronic illness, but not with sociodemographic characteristics. Students had a high stress perception but had relatively lower than depression and anxiety. Almost half of the students reported that they were moderately or severely depressed or anxious.

Conclusion
All MBI subscales had statistically significant correlation with scores of mental health or chronic physical illnesses. The respondents reported high percentages of all components of MBI. Prevalence of depression, anxiety, and stress is much higher in dental students compared to the general population. They also have a very high prevalence of all components of the MBI. Further research is warranted to explore additional factors contributing to burnout and mental health issues among dental students and to develop effective strategies for prevention and intervention.
Exploring the prognostic significance of blood carnitine and acylcarnitines in hepatitis C virus-induced hepatocellular carcinoma
Authors: Abbass Basuni Ashraf , Sheashaey Azza El , Fert Ashraf El , Obada Manar , Abdelsameea Eman , Abdel-Samiee Mohamed , Ibrahim Asmaa , Khalil Ashraf 
Published: March 2024

Abstract
Background
Hepatic energy metabolism is intricately linked with the metabolic changes associated with HCV infection and hepatocellular carcinoma (HCC). This study investigated the potential of carnitine and acylcarnitines as markers for monitoring the development and progression of HCC in the context of HCV-induced liver cirrhosis. Blood samples from patients with chronic liver cirrhosis due to HCV (n = 55) and from those with HCC (n = 90) were analyzed, alongside samples from healthy control subjects (n = 25), utilizing liquid chromatography coupled with mass spectrometry.

Results
Principal component analysis revealed distinct metabolic clustering patterns, segregating HCC and HCV patients into separate groups. Pairwise comparisons showed significantly elevated acylcarnitine levels in both HCV and HCC patients when compared to the control group (p = 0.001). Importantly, there was no significant difference between HCV and HCC groups, although linear trend analysis indicated an increasing linear trend that reached its peak in the HCC group, signifying a notable relationship with disease severity (p = 0.001).

Conclusion
The observed carnitine and acylcarnitine levels in HCV and HCC patients offer crucial clinical insights, suggesting their potential as valuable diagnostic and prognostic markers.
Formulation and evaluation of nanobiotherapeutics of Terminalia arjuna through plant tissue culture for atherosclerosis
Authors: Wadekar Pradnya Pradeep , Salunkhe Vijay Rajaram 
Published: March 2024

Abstract
Background
The study seeks to investigate the therapeutic potential of Terminalia arjuna callus in addressing atherosclerosis. In order to get maximum beneficial phytoconstituents from Terminalia arjuna, it is recommended to harvest the bark from Arjuna trees that are at least 15 years old and a gap of minimum 2 years should be kept before harvesting bark from the same plant. The callus culture technique was employed to expedite the process. The callus culture extract was subsequently converted into a nanosuspension with the aim of improving the efficacy of its phytoconstituents. It was then subjected to a comprehensive series of in vitro and in vivo evaluations to ascertain its potential for treatment of atherosclerosis.

Results
Liquid chromatography–mass spectrometry analysis of the callus extract confirmed the presence of flavonoids and terpenoids, known for their antioxidant and anti-inflammatory activities. Some terpenoids were even absent in Arjuna tree naturally. TEM images validated successful entrapment of the extract within the nanoparticles. In vitro analysis for antilipase and antioxidant assay confirmed the antiatherosclerotic potential of the extract. In vivo tests on rat blood serum demonstrated a significant reduction in total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and very low-density lipoprotein. Histopathological analysis of rat aortas showed additional confirmation of antiatherosclerotic action.

Conclusion
In conclusion, the study highlights the potential of nanosuspension derived from Terminalia arjuna callus extract as a comprehensive therapeutic strategy for atherosclerosis treatment. The research highlights antioxidant, anti-inflammatory, and antiatherosclerotic properties of the callus, hinting at its viability as a potential treatment for atherosclerosis. This interdisciplinary investigation emphasizes the promising role of traditional medicinal plants within modern medical paradigms.
Design, synthesis, 2D-QSAR, molecular dynamic simulation, and biological evaluation of topiramate–phenolic acid conjugates as PPARγ inhibitors
Authors: Padhy Ipsa , Banerjee Biswajit , Achary P. Ganga Raju , Gupta Pramodkumar P. , Sharma Tripti 
Published: March 2024

Abstract
Background
Obesity is a precursor for many co-morbid diseases. One of the main triggering factors for obesity is the abnormal expansion of white adipose tissue characterized by high rates of genesis and differentiation of precursor cells into mature adipocytes. As a result, targeting adipogenesis and adipogenic transcription factors opens new roadmaps for developing novel antiobesity pharmacotherapies. The present study was intended to rationally develop topiramate–phenolic acid conjugate for targeting obesity via inhibition of PPARγ which is often considered as the master regulator of adipogenesis.

Results
2D QSAR models were built to foretell PPARγ inhibitory activity of designed conjugates. The models presented excellent robustness, goodness of fit, and predictive capability compounds. The highest PPARγ inhibitory activity was predicted for T3 (topiramate–caffeic acid conjugate) with a pIC50 value of 7.08 µM. Molecular docking was performed for all the designed conjugates against PPARγ (PDB ID: 3VSO). The highest binding affinity was exhibited by T3 (− 11.27 kcal/mol) and displayed strong and stable interactions with the receptor within the allosteric pocket in comparison to the irreversible PPARγ antagonist, GW9662 (binding affinity, − 9.0 kcal/mol). These results were confirmed by subjecting the best-docked molecules to molecular dynamic simulations. The PPARγ–T3 complex was observed to be most stable with maximum number of hydrogen bonds (maximum observed RMSD = 0.57 Å at 100 ns) in comparison to PPARγ–topiramate and PPARγ–caffeic acid complexes. Consequently, T3 was synthesized and further subjected to in vitro screening. The TR-FRET assay established T3 as a PPARγ antagonist (IC50 = 6.78 µM). T3 also significantly reduced the lipid buildup in the 3T3-L1 adipocytes in a dose-dependent manner. In addition, T3 also reduced the protein expression levels of PPARγ as evidenced from western blot results.

Conclusions
Studies clearly indicated that T3 reduces adipose tissue cell differentiation by downstreaming PPARγ expression at protein levels, thereby emerging as a novel scaffold for antiobesity pharmacotherapy.

Graphical abstract