bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-06 Efficacy of Lutetium-Peptide Receptor Radionuclide Therapy and osilodrostat treatment at achiving eucortisolism and tumour stabilization in a patient with metastatic ectopic ACTH-syndrome
Authors: Khandaeva Patimat , Golounina Olga , Feidorov Ilia , Przhiyalkovskaya Elena , Mel’nichenko Galina , Belaya Zhanna 
Published: January 2024

Abstract

Introduction
Ectopic ACTH syndrome (EAS) is a rare cause of endogenous hypercortisolism. We present a case of a patient diagnosed with severe EAS, achieving eucortisolism and a favorable outcome of ACTH-producing metastatic pancreatic neuroendocrine tumor (NET) after 177Lu-DOTATATE and osilodrostat treatment.

Clinical Case
A female patient was admitted to our clinic at the age of 55 complaining of severe fatigue, facial and leg edema. Laboratory tests revealed a significant degree of ACTH-dependent hypercortisolemia (late-night serum cortisol 1856 nmol/L (64–327), late-night salivary cortisol (LNSC) 387.7 nmol/L (0.5–9.65), 24hUFC 8561 nmol/L (100–379), ACTH 332.8 pg/mL (7.2–63.3)), hypokalemia (1.88 mmol/L), increased liver enzymes (alanine aminotransferase (ALT) 303.2 U/L (0–55), aspartate aminotransferase (AST) 94.3 U/L (5–34)). MRI of the brain was negative for pituitary abnormalities. CT and somatostatin receptor scintigraphy with 99mTc-Tektrotyd revealed NET of the pancreas and multiple liver metastases. Subsequent biopsy confirmed NET grade 2, Ki67 – 7%. Treatment with lanreotide 120 mg every four weeks was initiated. In order to control hypercortisolism the patient received osilodrostat at a dose of 10 mg daily, which improved the patient's general condition in the first days of therapy. After 1 month of treatment, her hypercortisolism symptoms improved, LNSC dropped to 0.54 nmol/L and morning cortisol dropped from 1451 nmol/L (101–535) to 60.7 nmol/L, which could suggest adrenal insufficiency. She also had normalization of potassium and liver enzymes (ALT 18.4 U/L, AST 23 U/L). The dose of osilodrostat was firstly reduced and then discontinued. 177Lu-DOTATATE treatment was offered with four doses (7.4 GBq (200 mCi) every 8 weeks). The first dose was administered in January 2023. The SPECT-CT performed after the second dose demonstrated disease stabilization. At the time of writing, the patient remains in eucortisolism (LNSC 5,36 nmol/L, morning cortisol 140 nmol/L, ACTH 36.4 pg/ml) with tumor stabilisation after 4 doses of 177Lu-DOTATATE. However, the most recent routine blood test revealed thrombocytopenia (platelets 44×109/μl (150–400)), decreased white blood cell count (3.24×109/μl (4.5–11)), lymphocytes (0.71×109/μl (1.18–1.34)) and hemoglobin 98 g/L (117–160). Nevertheless, her general condition remains stable and significantly improved versus the initial investigation.

Conclusion
This observation highlights the feasibility and efficacy of a combined approach using osilodrostat and 177Lu-DOTATATE in the management of patients with metastatic ACTH-producing NET. This approach resulted in a substantially improved patient quality of life.
Funding Russian Scientific Foundation 19-15-00398
A Zika virus protein expression screen in Drosophila to investigate targeted host pathways during development
Authors: Link Nichole , Harnish J. Michael , Hull Brooke , Gibson Shelley , Dietze Miranda , Mgbike Uchechukwu E. , Medina-Balcazar Silvia , Shah Priya S. , Yamamoto Shinya 
Published: January 2024

ABSTRACT
In the past decade, Zika virus (ZIKV) emerged as a global public health concern. Although adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of disease caused by this virus, which includes microcephaly. In this study, we generated a toolkit to ectopically express ZIKV proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We used this toolkit to identify phenotypes and potential host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins caused scorable phenotypes, such as overall lethality, gross morphological defects, reduced brain size and neuronal function defects. We further used this system to identify strain-dependent phenotypes that may have contributed to the increased pathogenesis associated with the outbreak of ZIKV in the Americas in 2015. Our work demonstrates the use of Drosophila as an efficient in vivo model to rapidly decipher how pathogens cause disease and lays the groundwork for further molecular study of ZIKV pathogenesis in flies.
Case Report: Acquired hemophilia A following COVID-19 vaccine
Authors: Bouslama Emna , Ben Ismail Hajer , Zahra Kmira , Sassi Nadia , Dhaha Yossra , Bouatay Amina , Ben Boussef Yosra , Ben Sayed Nesrine , Regaieg Haifa , Khelif Abderrahim 
Published: January 2024

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and has subsequently been responsible for immense morbidity and mortality. This resulted in the development of vaccines in record time, potentially posing safety issues. Several cases of acquired hemophilia A (AHA) following coronavirus disease 2019 (COVID-19) vaccines have been described in the literature. AHA is a rare autoimmune disease due to the production of IgG autoantibodies to coagulation FVIII that burdens high morbidity and mortality. It is presumed mainly on identifying an increased activated partial thromboplastin time (aPTT), even without bleeding and is confirmed by determining a FVIII inhibitor. To the best of our knowledge, this is the first report of AHA after inactivated virus COVID-19 treated with low dose rituximab (RTX). Lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. Case presentation: We report a case of AHA occurring in a 69-year-old man 60 days after an inactivated Sinovac-coronavac COVID-19 vaccine. Diagnosis of AHA was based on clinical presentation and confirmed with prolonged activated partial thromboplastin time, Factor VIII deficiency and the presence of an FVIII inhibitor. Follow-up showed a significant clinical and biological improvement, aPTT was normalized as of 18 days of treatment with corticosteroids along with low dose rituximab. Conclusions: In the literature, the reported cases of AHA following COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-based COVID-19 vaccines. Here, AHA was presented following inactivated virus COVID-19 vaccine. AHA treated with low dose rituximab can limit occurrence of side effects and the cost of treatment.
In silico identification of quorum sensing inhibitors against LasR protein in a clinical isolate of multidrug resistant Pseudomonas aeruginosa DMC-27b
Authors: Siam Md. Hasanul Banna , Sirajee Ahmad Salman , Limon Md. Belayet Hasan , Hossain M. Anwar , Sultana Munawar 
Published: January 2024

Background: Pseudomonas aeruginosa is an opportunistic pathogen that uses quorum-sensing (QS) and biofilm formation to subvert antibiotic therapy. Antibiotic resistance has led to a demand for alternative methods of treatment, and destabilizing the LasR-OdDHL binding with inhibitors offers a potential solution. Methods: This study aimed to construct a homology model of the LasR protein using the genetic sequence of the P. aeruginosa DMC-27b strain (GenBank: SMRY00000000.2). Molecular docking, molecular mechanics-based binding free energy calculation, and pharmacokinetic analysis were performed on 1900 3D structures collected from synthetic and natural compound databases to identify three potential lead molecules. These compounds were evaluated using ADMET (absorption, distribution, metabolism, excretion, toxicity) analysis, and molecular dynamics protocols were used to refine the results. Results: The three lead compounds showed higher binding capability with the LasR receptor than the native ligand and passed the ADMET evaluation stage. In total, 44 properties remained within the range of 95% of known drugs, indicating their potential efficacy as drugs against P. aeruginosa and other bacteria that use a similar QS system. Conclusions: This study provides insights into potential drug designing and development against clinical isolates of emerging P. aeruginosa strains and other bacteria that use a similar QS system.
A cross-sectional study of the psychosocial and occupational impact of COVID-19 among NHS staff: findings from a Northwest London cohort during the second wave
Authors: Powell Richard A , Burmester Victoria ML , Waddingham Ed , Jesuthasan Jehanita , Norton John , Jayacodi Sandra , Guan Steven , Nicholls Dasha 
Published: January 2024

Background: Evidence of the deleterious mental health impact of COVID-19 on healthcare workers shows the priority need to support their psychological wellbeing. We assessed the nature, prevalence and factors associated with the psychosocial and occupational impact of COVID-19 among NHS staff during the pandemic. Methods: A cross-sectional online survey was sent to all NHS provider organisations in Northwest London in January 2021. Results: Of 1,065 participants completing the survey, 906 (85%) provided responses to the full survey. Over half (54.1%; n=543) exceeded the cut-off score for probable mental disorders, 31.1% (n=222) for probable burnout, and similarly for PTSD (28.5%; n=210). 28.6% (n=214) had experienced suicidal thoughts. 58% (n=429) scored >5 out of 10 for emotional and physical exhaustion. Over 30% (n=328) of respondents reported using some kind of staff support service. Staff in pay bands 4-6 were more likely to have common mental disorders (CMD) (OR 2.42 [1.20,4.88]) and PTSD symptoms (OR 4.18 [1.44,12.14]) than lower banded staff. Staff working in acute care settings were more likely to experience CMD (OR 1.50 [1.08,2.07]) and PTSD (OR 1.57 [1.03,2.41]) than in non-acute settings. Low social connectedness and perceived delivery of poor-quality care were highly associated with risk of all mental health problems, apart from alcohol misuse (OR range 1.56-18.34). Conclusions: Psychosocial morbidity and adverse occupational impacts on NHS staff in the second wave of the COVID-19 pandemic echoed that reported in the first wave. Social connection and perception of delivering good care were important, potentially modifiable, mitigating factors.
Iterative Rule Extension for Logic Analysis of Data: An MILP-Based Heuristic to Derive Interpretable Binary Classifiers from Large Data Sets
Authors: Balvert Marleen 
Published: January 2024

Data-driven decision making is rapidly gaining popularity, fueled by the ever-increasing amounts of available data and encouraged by the development of models that can identify nonlinear input–output relationships. Simultaneously, the need for interpretable prediction and classification methods is increasing as this improves both our trust in these models and the amount of information we can abstract from data. An important aspect of this interpretability is to obtain insight in the sensitivity–specificity trade-off constituted by multiple plausible input–output relationships. These are often shown in a receiver operating characteristic curve. These developments combined lead to the need for a method that can identify complex yet interpretable input–output relationships from large data, that is, data containing large numbers of samples and features. Boolean phrases in disjunctive normal form (DNF) are highly suitable for explaining nonlinear input–output relationships in a comprehensible way. Mixed integer linear programming can be used to obtain these Boolean phrases from binary data though its computational complexity prohibits the analysis of large data sets. This work presents IRELAND, an algorithm that allows for abstracting Boolean phrases in DNF from data with up to 10,000 samples and features. The results show that, for large data sets, IRELAND outperforms the current state of the art in terms of prediction accuracy. Additionally, by construction, IRELAND allows for an efficient computation of the sensitivity–specificity trade-off curve, allowing for further understanding of the underlying input–output relationship. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms–Discrete. Funding: This work was supported by the Netherlands Organization for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) [Grant VI.VENI.192.043]. Supplemental Material: The online supplement is available at https://doi.org/10.1287/ijoc.2021.0284 .
The Relationship Between Personality Factors, Vocational Identity and Career Decision-Making Self-Efficacy
Authors: Turda Sebastian 
Published: January 2024

Context: Adolescence is the training ground for adult life. In a relatively short period, the adolescent will undergo a metamorphosis. During the high school years, the majority of adolescents move from persistent dependence to true independence, from logical thinking to abstract, complex and hypothetical thinking, from impulsivity to consideration and from a diffuse feeling about one's own person to a reasonably defined self-identity. Adolescent's vocational identity formation during high school is an extremely important process in vocational and career counseling, because it helps them to make rational choices regarding the choice of a career gaining an increased level of career maturity.
Methods: The present study had as participants 300 Romanian teenagers which belong to the following paths of studies/profiles: formal sciences (specializations: Mathematics-informatics and Natural Sciences), services (specializations: Economics, trade, tourism and food) and humanities (specialization: Philology). The tools used in the adolescent evaluation process were Career Decision-Making Self-Efficacy-Short Form Scale (CDMSE-SF), the Vocational Identity Status Assessment (VISA) and the NEO Five-Factor Inventory (NEO-FFI-3).
Results: After the interpretation of the obtained results, the following aspects were demonstrated: The identity status career commitment correlates with the personality traits - neuroticism, extraversion, openness to experience and conscientiousness, and regarding the career decision-making self-efficacy it correlates with the self-evaluation process, obtaining information about self and professions, setting goals, career planning and the problem-solving process. Identity status identification with career commitment correlates with personality traits - extraversion, openness to experience and conscientiousness, and from the perspective of the career decision-making self-efficacy, it correlates with the process of self-evaluation, obtaining information about self and professions, setting goals, solving problems and career planning. The identity status career commitment flexibility correlates with the personality traits neuroticism and conscientiousness, and from the perspective of the career decision-making self-efficacy it correlates with the problem-solving process. Identity status career self-doubt correlates positively with the personality trait neuroticism and negatively with conscientiousness, the process of self-evaluation, obtaining information about self and professions, setting goals, career planning and problem solving.
Conclusion: The main purpose of this study was to investigate the relationship between vocational identity, personality factors and career decision-making self-efficacy. The results demonstrated that certain personality traits, respectively certain components of career decision-making self-efficacy are predictors for the adolescent's vocational identity formation.
Two risk factors for hypozincemia in diabetic β-thalassemia patients: Hepatitis C and deferasirox
Authors: Darvishi-Khezri Hadi , Karami Hossein , Naderisorki Mohammad , Ghazaiean Mobin , Kosaryan Mehrnoush , Mosanejad-Galchali Amir , Aliasgharian Aily , Karami Hasan 
Published: January 2024

Background and aim
Hypozincemia is a prevalent adverse consequence in diabetes mellitus (DM) and β-Thalassemia patients. We aimed to evaluate the level of serum zinc in β-thalassemia patients with DM and a risk assessment for hypozincemia.

Methods
The study population included transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) with overt DM (fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-h plasma glucose≥200 mg/dL). Serum zinc concentration was measured by the colorimetric method, and the values below 70 μg/dL were defined as hypozincemia. Myocardial and liver T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) were valued by a free contrast MRI. The demographic, clinical, paraclinical, and laboratory data were also recorded. The data belonged to the period from December 2018 until December 2020.

Results
Of 64 diabetic β-thalassemia patients, 41 cases had zinc data in their medical files (aged 38 ± 9 years, 48.8% female). 78.05% of patients (n = 32) were TDT, and 21.95% were NTDT (n = 9). The mean ± standard deviation of zinc level was 110.2 ± 127.6 μg/dL. The prevalence of hypozincemia was 9.76%, 95% confidence interval [CI] 0.27 to 19.24 (four cases). After controlling age, the odds of hypozincemia for using deferasirox (DFX) was 8.77, 95% CI 0.60 to 127.1. In β-thalassemia patients, the age-adjusted risk of hypozincemia was calculated at 15.85, 95% CI 0.47 to 529.3 for hepatitis C. The adjusted risk of hypozincemia based on age for antacid use was 6.34, 95% CI 0.39 to 102.7.

Conclusion
In light of this study, as well as hepatitis C, using DFX and antacids is associated with a high risk of hypozincemia amid diabetic β-thalassemia cases. However, upward bias should be taken into consideration.
Monitoring SARS-CoV-2 genetic variability: A post-market surveillance workflow for combined bioinformatic and laboratory evaluation of commercial RT-PCR assay performance
Authors: Kosińska-Selbi Barbara , Kowalczyk Justyna , Pierscińska Jagoda , Wełeszczuk Jarosław , Peñarrubia Luis , Turner Benjamin , Pareja Josep , Porco Roberto , Diaz-Hernandez Rubi , Juanola-Falgarona Martí , Rey Melisa , Manissero Davide , Blacha Anna 
Published: January 2024

Objective
The speed at which Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is mutating has made it necessary to frequently assess how these genomic changes impact the performance of diagnostic real-time polymerase chain reaction (RT-PCR) assays. Herein, we describe a generic three-step workflow to assess the effect of genomic mutations on inclusivity and sensitivity of RT-PCR assays.

Methods
Sequences collected from the Global Initiative on Sharing All Influenza Data (GISAID) were mapped to a SARS-CoV-2 reference genome to evaluate the position and prevalence of mismatches in the oligonucleotide-binding sites of the QIAstat-Dx, an RT-PCR panel designed to detect SARS-CoV-2. The frequency of mutations and their impact on melting temperature were assessed, and sequences flagged by risk-based criteria were examined in vitro.

Results
Out of 8,900,393 SARS-CoV-2 genome sequences analyzed, only 173 (0.0019%) genomes contained potentially critical mutations for the QIAstat-Dx; follow-up in-vitro testing confirmed no impact on the assays’ performance.

Conclusions
The current study demonstrates that SARS-CoV-2 genetic variants do not affect the performance of the QIAstat-Dx device. It is recommended that manufacturers incorporate this workflow into obligatory post-marketing surveillance activities, as this approach could potentially enhance genetic monitoring of their product.
The impact of the newly developed school-based ‘Digital Health Contact’—Evaluating a health and wellbeing screening tool for adolescents in England
Authors: Porter Alice , d’Apice Katrina , Albers Patricia , Woodrow Nicholas , Fairbrother Hannah , Breheny Katie , Mills Clare , Tebbett Sarah , De Vocht Frank 
Published: January 2024

Introduction
Supporting adolescents with their health and wellbeing is an international public health priority. Schools are well placed to universally detect unmet health needs and support pupils. This study aimed to evaluate the effectiveness of a digital health and wellbeing screening tool, called the ‘Digital Health Contact’ (DHC) implemented in schools in the East Midlands of England. The DHC, delivered by Public Health Nurses (School Nurses) (PHN(SN)), aims to identify pupils with unmet health needs (via a ‘red flag’ system) and provide appropriate support.

Materials and methods
Using data from 22 schools which took part in the DHC and 14 schools which did not take part, across three academic years (2018–2020), we conducted a controlled interrupted timeseries analysis with negative binomial regression to explore the effect of the DHC on the number of annual referrals to PHN(SN). Using DHC data from 164 pupils, we further conducted a Difference-in-Difference analysis to explore the impact of ‘red flag’ and referral via the DHC in Year 9 (age 13–14) on the number of red flags in Year 11 (age 15–16).

Results
Across all schools, the mean annual number of referrals increased over the three year follow-up period. In the adjusted model, the number of referrals was comparable between schools taking part in the DHC and non-participating schools (0.15 referrals [95% CI -0.21, 0.50]). Red flag score was not significantly different among Year 11 pupils, after being referred via the DHC in Year 9 (-0.36 red flags [95% CI -0.97, 0.24]).

Discussion
The DHC, and similar screening tools, have the potential to raise awareness of the health and wellbeing support in schools and provide an additional pathway of referral to this support for pupils with unmet health needs, without replacing the traditional pathway where pupils refer themselves or are referred by teachers.
Algeria’s Strategic Position and Its Implications for the Development of China- Algeria Relations
Authors: Huang Hui , Liu Jing 
Published: January 2024

Abstract
Algeria is an important country in Africa and the Middle East, which plays an active role in African affairs. Since the founding of the People’s Republic of China, it has maintained a harmonious and friendly relationship with Algeria. In 2014, Algeria became the first Arab country with which China established a comprehensive strategic partnership. Within the framework of China-Algeria comprehensive strategic partnership, the two sides have broad space for cooperation in regional and international affairs. The development of China- Algeria relations is conducive to raising friendly cooperative relations between China and Arab and African countries to a new level, and to the advancement of the Belt and Road Initiative in the Middle East and Africa.