bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug resistance in children and adolescents with HIV in Panama
Authors: Ventosa-Cubillo Judit , Pinzón Ramón , González-Alba José María , Estripeaut Dora , Navarro María Luisa , Holguín África 
Published: December 2022

Abstract

Objectives
The inadequacy of resistance monitoring in Latin America leads to circulation of HIV strains with drug resistance mutations (DRMs), compromising ART effectiveness. This study describes the DRM prevalence in HIV-infected paediatric patients in Panama.

Methods
During 2018–19, plasma was collected from 76 HIV-infected children/adolescents (5 ART-naive, 71 treated) in Panama for HIV-1 DRM pol analysis, predicted antiretroviral (ARV) susceptibility by Stanford, and HIV-1 variant phylogenetic characterization.

Results
HIV-1 pol sequences were recovered from 67 (88.2%) of 76 children/adolescents (median age 12 years), carrying 65 subtype B, 1 subtype G and 1 unique recombinant URF_A1B. Five were ART-naive and 62 ART-treated under virological failure (viraemia &gt;50 copies/mL) with previous exposure to NRTIs, (100%), NNRTIs (45.2%), PIs (95.2%) and integrase strand transfer inhibitors (INSTIs, 17.7%). Among the treated patients, 34 (54.8%) carried resistant strains, with major DRMs to one (40.3%), two (9.7%) or three (4.8%) ARV families. Most of them harboured DRMs to NRTIs (58.5%) or NNRTIs (39%), but also major DRMs to PIs (4.9%) and INSTIs (6.5%). We also found dual-class NRTI + NNRTI (12.2%) and NNRTI + PI (2.6%) resistance. Two naive subjects carried viruses with DRMs to NRTIs and NRTI + NNRTI, respectively. Sequenced viruses presented high/intermediate resistance mainly to emtricitabine/lamivudine (48.9% each) and efavirenz/nevirapine (33.3% each). Most participants were susceptible to PIs (91.3%) and INSTIs (88.1%).

Conclusions
The high DRM prevalence to NRTIs and NNRTIs observed among treated HIV-infected children/adolescents in Panama justifies the need for routine resistance monitoring for optimal rescue therapy selection in this vulnerable population.
Modeling the impact of data sharing on variant classification
Authors: Casaletto James , Cline Melissa , Shirts Brian 
Published: December 2022

AbstractObjectiveMany genetic variants are classified, but many more are variants of uncertain significance (VUS). Clinical observations of patients and their families may provide sufficient evidence to classify VUS. Understanding how long it takes to accumulate sufficient patient data to classify VUS can inform decisions in data sharing, disease management, and functional assay development.Materials and MethodsOur software models the accumulation of clinical evidence (and excludes all other types of evidence) to measure their unique impact on variant interpretation. We illustrate the time and probability for VUS classification when laboratories share evidence, when they silo evidence, and when they share only variant interpretations.ResultsUsing conservative assumptions for frequencies of observed clinical evidence, our models show the probability of classifying rare pathogenic variants with an allele frequency of 1/100 000 increases from less than 25% with no data sharing to nearly 80% after one year when labs share data, with nearly 100% classification after 5 years. Conversely, our models found that extremely rare (1/1 000 000) variants have a low probability of classification using only clinical data.DiscussionThese results quantify the utility of data sharing and demonstrate the importance of alternative lines of evidence for interpreting rare variants. Understanding variant classification circumstances and timelines provides valuable insight for data owners, patients, and service providers. While our modeling parameters are based on our own assumptions of the rate of accumulation of clinical observations, users may download the software and run simulations with updated parameters.ConclusionsThe modeling software is available at https://github.com/BRCAChallenge/classification-timelines.
Fingerprints: A New Specimen for Innovative Applications for the Detection of Xenobiotics
Authors: Ameline Alice , Gheddar Laurie , Arbouche Nadia , Raul Jean-Sébastien , Kintz Pascal 
Published: December 2022

Abstract
Fingerprints are invisible traces that result from a deposition of sweat and sebum present on the papillary ridges. As sweat and sebum contain drugs, fingerprints are promising since collection is rapid, non-invasive and difficult to falsify. Very limited data are available in the literature, and therefore, it seems opportune to study the transfer of xenobiotics onto the items taken in hand via the fingerprints. Two studies were implemented using the ballpoint pen as a model. The objective of the first study was to compare the nicotine concentrations found on the pens of three smokers and three non-smokers. Five pens, belonging to each subject and used regularly, were rubbed with a cotton swab dipped in methanol and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC–MS-MS). The second study was to analyze the transfer via fingerprints of four volunteers, after administration of 30 mg of codeine. The objective was to determine the feasibility of this study and the time corresponding to the highest concentration of codeine. Over a 24-h period, new pens were handled for 5 min by the four volunteers, rubbed with a cotton swab dipped in methanol, and then analyzed by LC–MS-MS. The nicotine study showed a major difference between the nicotine concentrations obtained from smokers (between 6 and 276 ng/pen) and non-smokers (between 2 and 4 ng/pen). After administration of 30 mg of codeine, the analysis of the pens of the four volunteers allowed to demonstrate the presence of codeine up to 24 h between 9 and 544 pg/pen. Normal hygiene practices did not influence the final result. The highest concentration was observed after 2 h. Morphine was also detected (between 19 and 33 pg/pen). These preliminary results should be considered a demonstration of the interest of fingerprints testing to document drug exposure.
Synthetic Cathinones in Belgium: Two Case Reports with Different Outcomes Observed in the Emergency Room
Authors: Deville M , Fedorowicz R , Grandjean F , Simon M , Charlier C 
Published: December 2022

Abstract
We herein report two cases of cathinone intoxication. The first case is about a drug addict who was admitted to the emergency room after the injection of an unknown compound. He presented with tachycardia, palpitations, mydriasis, dyspnea, dizziness, headache and nausea. After leaving the hospital against medical advice, he returned the next day with police escort, presenting aggressiveness and agitation signs. One month later, he returned one more time for sleeping disorders, hallucinations and anxiety. He was finally transferred for his 21st detoxification treatment. The second case concerns a man who was wandering the streets and tried to escape when police officers called him. He confessed to snorting of N-ethylpentedrone and was admitted with severe agitation including delusion of persecution, tachycardia, mydriasis and fever. Because of renal failure, rhabdomyolysis and metabolic acidosis, he was transferred to the intensive care unit where he manifested worsening of the symptoms, turning into coma. He was intubated for 3 days before a complete resolution of the symptoms. A screening was performed by high-resolution mass spectrometry followed by quantifications made by high-performance liquid chromatography coupled with a diode array detector. In the first case, alpha-pyrrolidinohexiophenone was identified only during the first two admissions. However, as plenty of other psychotropic substances were also found, the cathinone alone could not be held directly responsible for the symptoms. In the second case, more than 2,000 ng/mL of N-ethylpentedrone was found without any decrease in the next 17 h, underlining the long half-life of this compound. Unlike the first case, symptoms could be clearly attributed to the cathinone. In conclusion, cathinones can be found on the Belgian illicit drug market, with various routes of administration and clinical consequences. In these two case reports, some common points were observed initially. However, one patient was finally able to leave the hospital without any treatment, whereas the other would most likely have died without intensive care.
Is Amnesty International Still a Grassroots, Member-Led Organization? An Assessment of Its Democratic Viability
Authors: O’Dell Roni Kay Marie , Veazey Linda 
Published: December 2022

Abstract
Amnesty International’s (AI) democratic organizational structure sets it apart from other human rights organizations in terms of member-led governance and policymaking, but professionalization trends and organizational consolidation challenge AI’s founding democratic principles. This article assesses AI’s continued democratic viability by analysing changes to its governance and policymaking procedures at the AI United States section level as well as the AI international secretariat. Semi-structured interviews and document analysis show that AI’s democratic structure remains strong because of what this article calls the leadership-member-volunteer nexus rather than because of rule-based interaction, legitimacy, or path dependence.
Study design considerations for trials to evaluate multicancer early detection assays for clinical utility
Authors: Minasian Lori M , Pinsky Paul , Katki Hormuzd A , Dickherber Tony , Han Paul K J , Harris Lyndsay , Patriotis Christos , Srivastava Sudhir , Weil Carol J , Prorok Philip C , Castle Philip E 
Published: December 2022

AbstractBlood-based assays using various technologies and biomarkers are in commercial development for the purpose of detecting multiple cancer types concurrently at an early stage of disease. These multicancer early detection (MCED) assays have the potential to improve the detection of cancers, particularly those for which no current screening modality exists. However, the unknown clinical benefits and harms of using MCED assays for cancer screening necessitate the development and implementation of a randomized controlled trial (RCT) to ascertain their clinical effectiveness. This was the consensus of experts at a National Cancer Institute–hosted workshop to discuss initial design concepts for such a trial. Using these assays to screen simultaneously for multiple cancers poses novel uncertainties for patient care compared with conventional screening tests for single cancers, such as establishing the diagnostic workup to confirm the presence of cancer at any organ site; clarifying appropriate follow-up for a positive assay for which there is no definitive diagnosis; identifying potential harms such as overdiagnosis of indolent disease; determining clinically effective and efficient strategies for disseminating MCED screening in real-world practice; and understanding the ethical implications, such as potentially alleviating or exacerbating existing health disparities. These assays present new and complex challenges for designing an RCT. Issues that emerged from the meeting centered around the need for a flexibly designed, clinical utility RCT to rigorously capture the evidence required to fully understand the net benefit of this promising technology. Specific topic areas were endpoints, screening protocols, recruitment, diagnostic pathway, pilot phase, data elements, specimen collection, and ethical considerations.
The manufacturing of 3D-printed microfluidic chips to analyse the effect upon particle size during the synthesis of lipid nanoparticles
Authors: Weaver Edward , Mathew Essyrose , Caldwell Jay , Hooker Andrew , Uddin Shahid , Lamprou Dimitrios A 
Published: December 2022

Abstract

Objectives
The process of 3D printing to produce microfluidic chips is becoming commonplace, due to its quality, versatility and newfound availability. In this study, a UV liquid crystal display (LCD) printer has been implemented to produce a progression of microfluidic chips for the purpose of liposomal synthesis. The emphasis of this research is to test the limitations of UV LCD printing in terms of resolution and print speed optimisation for the production of microfluidic chips.

Key findings
By varying individual channel parameters such as channel length and internal geometries, the essential channel properties for optimal liposomal formulation are being investigated to act as a basis for future experimentation including the encapsulation of active pharmaceutical ingredients. Using the uniquely designed chips, liposomes of ≈120 nm, with polydispersity index values of ≤0.12 are able to be reproducibly synthesised.

Conclusions
The influence of total flow rates and lipid choice is investigated in depth, to provide further clarification on how a microfluidic setup should be optimised. In-depth explanations of the importance of each channel parameter are also explained throughout, with reference to their importance for the properties of a successful liposome.
Evaluation of OrthoChromic OC-1 films for photon radiotherapy application
Authors: Lim Seng Boh , Tang Grace 
Published: December 2022

Abstract
A new film dosimetry system consists of the new OrthoChromic™ OC-1 film, and a novel calibration procedure was evaluated. Two films, C1 and C2, were exposed simultaneously using the 6FFF beam with a step-wedge pattern of five steps ranging from 590 to 3000 cGy. C1 was used for calibration, and C2 was used for calibration curve validation. The second scan of C2 was done by rotating the film by 90-deg. To evaluate the effectiveness of the non-uniform scanner response correction with the new system, a film was exposed to a 20 × 20 cm2 field. The beam profile measured with the film was compared to the IBA cc04 measurements in water. Films were irradiated to characterize the energy response, dynamic range and temporal growth effect. Open (MLC-defined) and clinical fields were radiated to evaluate the overall performance of the new system. The new calibration procedure was validated with an average dose difference of 1.6% and a gamma (2%,2 mm) passing rate of 100%. With C2 scanned 90-deg rotated, the average dose difference was 1.3%. The average difference between cc04 and film was 0.4%. The St between films and diode/cc04 were within −0.3% difference for 1 × 1 to 14 × 14 cm2 and −2.8% for 0.5 × 0.5 cm2. For clinical fields, the average gamma (3%,2 mm) was 98.8%. These results were consistent with EBT3 film and MapCheck measurements with a dose &gt; 400 cGy. The results have shown that the OC-1 film system can achieve accurate results for QA measurements, but more considerable uncertainty was observed within the low dose range.
A three-step process of manganese acquisition and storage in the microalgaChlorella sorokiniana
Authors: Vojvodić Snežana , Dimitrijević Milena , Žižić Milan , Dučić Tanja , Aquilanti Giuliana , Stanić Marina , Zechmann Bernd , Danilović Luković Jelena , Stanković Dalibor , Opačić Miloš , Morina Arian , Pittman Jon K , Spasojević Ivan 
Published: December 2022

AbstractMetabolism of metals in microalgae and adaptation to metal excess are of significant environmental importance. We report a three-step mechanism that the green microalga Chlorella sorokiniana activates during the acquisition of and adaptation to manganese (Mn), which is both an essential trace metal and a pollutant of waters. In the early stage, Mn2+ was mainly bound to membrane phospholipids and phosphates in released mucilage. The outer cell wall was reorganized and lipids were accumulated, with a relative increase in lipid saturation. Intracellular redox settings were rapidly altered in the presence of Mn excess, with increased production of reactive oxygen species that resulted in lipid peroxidation and a decrease in the concentration of thiols. In the later stage, Mn2+ was chelated by polyphosphates and accumulated in the cells. The structure of the inner cell wall was modified and the redox milieu established a new balance. Polyphosphates serve as a transient Mn2+ storage ligand, as proposed previously. In the final stage, Mn was stored in multivalent Mn clusters that resemble the structure of the tetramanganese–calcium core of the oxygen-evolving complex. The present findings elucidate the bioinorganic chemistry and metabolism of Mn in microalgae, and may shed new light on water-splitting Mn clusters.
Structural basis of transcription regulation by CNC family transcription factor, Nrf2
Authors: Sengoku Toru , Shiina Masaaki , Suzuki Kae , Hamada Keisuke , Sato Ko , Uchiyama Akiko , Kobayashi Shunsuke , Oguni Asako , Itaya Hayato , Kasahara Kota , Moriwaki Hirotomo , Watanabe Chiduru , Honma Teruki , Okada Chikako , Baba Shiho , Ohta Tsutomu , Motohashi Hozumi , Yamamoto Masayuki , Ogata Kazuhiro 
Published: December 2022

Abstract
Several basic leucine zipper (bZIP) transcription factors have accessory motifs in their DNA-binding domains, such as the CNC motif of CNC family or the EHR motif of small Maf (sMaf) proteins. CNC family proteins heterodimerize with sMaf proteins to recognize CNC–sMaf binding DNA elements (CsMBEs) in competition with sMaf homodimers, but the functional role of the CNC motif remains elusive. In this study, we report the crystal structures of Nrf2/NFE2L2, a CNC family protein regulating anti-stress transcriptional responses, in a complex with MafG and CsMBE. The CNC motif restricts the conformations of crucial Arg residues in the basic region, which form extensive contact with the DNA backbone phosphates. Accordingly, the Nrf2–MafG heterodimer has approximately a 200-fold stronger affinity for CsMBE than canonical bZIP proteins, such as AP-1 proteins. The high DNA affinity of the CNC–sMaf heterodimer may allow it to compete with the sMaf homodimer on target genes without being perturbed by other low-affinity bZIP proteins with similar sequence specificity.
Wheat EARLY FLOWERING 3 affects heading date without disrupting circadian oscillations
Authors: Wittern Lukas , Steed Gareth , Taylor Laura J , Ramirez Dora Cano , Pingarron-Cardenas Gabriela , Gardner Keith , Greenland Andy , Hannah Matthew A , Webb Alex A R 
Published: December 2022

Abstract
Plant breeders have indirectly selected for variation at circadian-associated loci in many of the world's major crops, when breeding to increase yield and improve crop performance. Using an eight-parent Multiparent Advanced Generation Inter-Cross (MAGIC) population, we investigated how variation in circadian clock-associated genes contributes to the regulation of heading date in UK and European winter wheat (Triticum aestivum) varieties. We identified homoeologues of EARLY FLOWERING 3 (ELF3) as candidates for the Earliness per se (Eps) D1 and B1 loci under field conditions. We then confirmed a single-nucleotide polymorphism within the coding region of TaELF3-B1 as a candidate polymorphism underlying the Eps-B1 locus. We found that a reported deletion at the Eps-D1 locus encompassing TaELF3-D1 is, instead, an allele that lies within an introgression region containing an inversion relative to the Chinese Spring D genome. Using Triticum turgidum cv. Kronos carrying loss-of-function alleles of TtELF3, we showed that ELF3 regulates heading, with loss of a single ELF3 homoeologue sufficient to alter heading date. These studies demonstrated that ELF3 forms part of the circadian oscillator; however, the loss of all homoeologues was required to affect circadian rhythms. Similarly, loss of functional LUX ARRHYTHMO (LUX) in T. aestivum, an orthologue of a protein partner of Arabidopsis (Arabidopsis thaliana) ELF3, severely disrupted circadian rhythms. ELF3 and LUX transcripts are not co-expressed at dusk, suggesting that the structure of the wheat circadian oscillator might differ from that of Arabidopsis. Our demonstration that alterations to ELF3 homoeologues can affect heading date separately from effects on the circadian oscillator suggests a role for ELF3 in cereal photoperiodic responses that could be selected for without pleiotropic deleterious alterations to circadian rhythms.
Predictors of weight loss during the intensive phase of tuberculosis treatment in patients with drug-susceptible pulmonary tuberculosis in South India
Authors: Kalva Jayashree , Babu Senbagavalli P , Narasimhan Prakash B , Raghupathy Kalaivani , Ezhumalai Komala , Knudsen Selby , Horsburgh Charles R , Hochberg Natasha , Salgame Padmini , Roy Gautam , Ellner Jerrold , Sarkar Sonali 
Published: December 2022

Abstract

Background
Tuberculosis (TB) is well-known for causing wasting. Patients on treatment gain weight and weight loss is associated with unfavorable treatment outcomes. There is limited description of weight loss and its predictors during intensive treatment phase. The objective of this study was to assess the predictors of weight loss during intensive phase and to see if there is any association exists with sputum conversion at the end of intensive phase of treatment.

Methods
Data collected as a part of the prospective TB cohort (Regional Prospective Observational Research for TB India Phase 1) conducted in Pondicherry, Cuddalore and Viluppuram districts of Tamil Nadu were used for this study. Sputum smear and body weight comparison were made in the baseline and at the end of second month of treatment.

Results
In all, 726 participants had weight measurements at the two time points and 18.7% had weight loss; mean weight lost being 2.3 kg (SD 3.05). Mean weight loss was more among males (2.4 kg, SD 3.2), diabetics (2.8 kg, SD 3.9) and alcoholics (2.1 kg, SD 2.4). Alcohol consumption was the only predictor of weight loss after adjusting for age, diabetes, marital status and BMI (aRR 1.52, P 0.02). Weight loss was not associated with sputum conversion at the end of second month.

Conclusions
Alcohol use emerged as the major predictor for weight loss during intensive phase.
Finding the common ground: toward an inclusive approach to humanitarian crisis
Authors: Corpuz Jeff Clyde G 
Published: December 2022

Abstract
A recently published correspondence proposed a solution for survival in the context of Indonesia using a spiritual-philosophical perspective to fight the pandemic crisis. However, such principle can be too exclusive and restrictive in its application to the pandemic crisis. One must also consider the alternative approaches in solving the crisis from a multidisciplinary and multisectoral approach. This paper proposes the principle of ‘human dignity’ as an inclusive approach to humanitarian crisis.