bluuebunny/crossref_metadata_2025 huggingface dataset:
Methadone’s Resurgence in Bridging the Treatment Gap in the Overdose Crisis: Position Statement of AMERSA, Inc (Association for Multidisciplinary Education, Research, Substance Use, and Addiction)
Authors: Suen Leslie W. , Incze Michael , Simon Caty , Englander Honora , Bratberg Jeffrey , Groves Scott Gail , Winograd Rachel
Published: May 2024

Background:

The United States is grappling with an unprecedented overdose crisis, exacerbated by the proliferation of potent synthetic opioids like illicitly manufactured fentanyl. Despite the efficacy of methadone treatment in managing opioid use disorder, regulatory barriers hinder its widespread utilization. This article examines the complex landscape of methadone regulation across federal, state, and local levels, highlighting disparities and opportunities for reform.

Issue:

The COVID-19 public health emergency prompted temporary flexibility in methadone regulations, including expanded take-home doses and telehealth counseling, leading to improved treatment experiences and retention. Permanent revisions to federal guidelines have since been introduced by the Substance Abuse and Mental Health Services Administration, reflecting a progressive shift toward patient-centered care and streamlined access. State regulations, managed by Single State Agencies and State Opioid Treatment Authorities, vary widely, often imposing additional restrictions that impede access to methadone treatment. Local OTP clinics further exacerbate barriers through stringent policies, despite federal and state guidelines advocating for flexibility.

Recommendations:

Coordinated efforts among policymakers, healthcare providers, and communities are needed to promote the development of accountability measures, incentives, and community involvement to ensure equitable access and quality of care. To truly meet the demand needed to end the existing overdose crisis and enhance accessibility and comprehensive healthcare services, methadone treatment expansion beyond traditional OTP settings into primary care offices and community pharmacies should take place.
Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle
Authors: Johnson Carys S. , Williams Matthew , Sham Kendig , Belluschi Serena , Ma Wenjuan , Wang Xiaonan , Lau Winnie W. Y. , Kaufmann Kerstin B. , Krivdova Gabriela , Calderbank Emily F. , Mende Nicole , McLeod Jessica , Mantica Giovanna , Li Juan , Grey-Wilson Charlotte , Drakopoulos Michael , Basheer Shaaezmeen , Sinha Shubhankar , Diamanti Evangelia , Basford Christina , Wilson Nicola K. , Howe Steven J. , Dick John E. , Göttgens Berthold , Green Anthony R. , Francis Natalie , Laurenti Elisa
Published: May 2024

Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols that rely on culture. However, the kinetics and mechanisms through which this occurs remain incompletely characterized. In this study, through time-resolved single-cell RNA sequencing, matched in vivo functional analysis, and the use of a reversible in vitro system of early G1 arrest, we defined the sequence of transcriptional and functional events that occur during the first ex vivo division of human LT-HSCs. We demonstrated that the sharpest loss in LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limit the global variability in gene expression, and transiently upregulate gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programs in culture. However, contrary to the current assumptions, we demonstrated that the loss of HSC function ex vivo is independent of cell cycle progression. Finally, we showed that targeting LT-HSC adaptation to culture by inhibiting the early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrated that controlling early LT-HSC adaptation to ex vivo culture, for example, via JAK inhibition, is critically important to improve HSC gene therapy and expansion protocols.
Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax
Authors: Walker Steven , Hallifax Robert , Ricciardi Sara , Fitzgerald Deirdre , Keijzers Marlies , Lauk Olivia , Petersen Jesper , Bertolaccini Luca , Bodtger Uffe , Clive Amelia , Elia Stefano , Froudarakis Marios , Janssen Julius , Lee Y.C. Gary , Licht Peter , Massard Gilbert , Nagavci Blin , Neudecker Jens , Roessner Eric , Van Schil Paul , Waller David , Walles Thorsten , Cardillo Giuseppe , Maskell Nick , Rahman Najib
Published: May 2024

Background

The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP.

Methods

This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations.

Results

The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis.

Conclusions

With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.
Brain structural and functional abnormalities associated with acute post-traumatic headache: iron deposition and functional connectivity
Authors: Nikolova Simona , Chong Catherine , Li Jing , Wu Teresa , Dumkrieger Gina , Ross Katherine , Starling Amaal , Schwedt Todd J.
Published: May 2024

Background

The purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI.

Methods

Sixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T2* maps and resting-state functional connectivity imaging. Between group T2* differences were determined using T-tests (p < 0.005, cluster size threshold of 90 voxels). For regions with T2* differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p < 0.05 with family wise error correction for multiple comparisons).

Results

The acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T2* values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T2* in the left posterior cingulate with SCAT symptom severity score (p = 0.05) and T2* in the left cuneus with headache frequency (p = 0.04).

Conclusions

Iron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T2* (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH.
Sequencing accuracy and systematic errors of nanopore direct RNA sequencing
Authors: Liu-Wei Wang , van der Toorn Wiep , Bohn Patrick , Hölzer Martin , Smyth Redmond P. , von Kleist Max
Published: May 2024

Background

Direct RNA sequencing (dRNA-seq) on the Oxford Nanopore Technologies (ONT) platforms can produce reads covering up to full-length gene transcripts, while containing decipherable information about RNA base modifications and poly-A tail lengths. Although many published studies have been expanding the potential of dRNA-seq, its sequencing accuracy and error patterns remain understudied.

Results

We present the first comprehensive evaluation of sequencing accuracy and characterisation of systematic errors in dRNA-seq data from diverse organisms and synthetic in vitro transcribed RNAs. We found that for sequencing kits SQK-RNA001 and SQK-RNA002, the median read accuracy ranged from 87% to 92% across species, and deletions significantly outnumbered mismatches and insertions. Due to their high abundance in the transcriptome, heteropolymers and short homopolymers were the major contributors to the overall sequencing errors. We also observed systematic biases across all species at the levels of single nucleotides and motifs. In general, cytosine/uracil-rich regions were more likely to be erroneous than guanines and adenines. By examining raw signal data, we identified the underlying signal-level features potentially associated with the error patterns and their dependency on sequence contexts. While read quality scores can be used to approximate error rates at base and read levels, failure to detect DNA adapters may be a source of errors and data loss. By comparing distinct basecallers, we reason that some sequencing errors are attributable to signal insufficiency rather than algorithmic (basecalling) artefacts. Lastly, we generated dRNA-seq data using the latest SQK-RNA004 sequencing kit released at the end of 2023 and found that although the overall read accuracy increased, the systematic errors remain largely identical compared to the previous kits.

Conclusions

As the first systematic investigation of dRNA-seq errors, this study offers a comprehensive overview of reproducible error patterns across diverse datasets, identifies potential signal-level insufficiency, and lays the foundation for error correction methods.
RHC genotyping in Chinese Han population
Authors: Shao Lin-Nan , Zheng Zi-Wei , Zhou Shi-Hang , Song Wen-Qian , Xia Yue-Xin , Liang Xiao-Hua
Published: May 2024

Background

The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population.

Methods

In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D− were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and −292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test.

Results

The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%).

Conclusions

None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.
Maintenance of bacterial outer membrane lipid asymmetry: insight into MlaA
Authors: Kaur M. , Mingeot -Leclercq M.-P.
Published: May 2024

The outer membrane (OM) of Gram-negative bacteria acts as an effective barrier to protect against toxic compounds. By nature, the OM is asymmetric with the highly packed lipopolysaccharide (LPS) at the outer leaflet and glycerophospholipids at the inner leaflet. OM asymmetry is maintained by the Mla system, in which is responsible for the retrograde transport of glycerophospholipids from the OM to the inner membrane. This system is comprised of six Mla proteins, including MlaA, an OM lipoprotein involved in the removal of glycerophospholipids that are mis-localized at the outer leaflet of the OM. Interestingly, MlaA was initially identified - and called VacJ - based on its role in the intracellular spreading of Shigella flexneri.

Many open questions remain with respect to the Mla system and the mechanism involved in the translocation of mislocated glycerophospholipids at the outer leaflet of the OM, by MlaA. After summarizing the current knowledge on MlaA, we focus on the impact of mlaA deletion on OM lipid composition and biophysical properties of the OM. How changes in OM lipid composition and biophysical properties can impact the generation of membrane vesicles and membrane permeability is discussed. Finally, we explore whether and how MlaA might be a candidate for improving the activity of antibiotics and as a vaccine candidate.

Efforts dedicated to understanding the relationship between the OM lipid composition and the mechanical strength of the bacterial envelope and, in turn, how such properties act against external stress, are needed for the design of new targets or drugs for Gram-negative infections.
Genome characterisation and comparative analysis of Schaalia dentiphila sp. nov. and its subspecies, S. dentiphila subsp. denticola subsp. nov., from the human oral cavity
Authors: Tian Xuechen , Teo Wee Fei Aaron , Yang Yixin , Dong Linyinxue , Wong Aloysius , Chen Li , Ahmed Halah , Choo Siew Woh , Jakubovics Nicholas S. , Tan Geok Yuan Annie
Published: May 2024

Background

Schaalia species are primarily found among the oral microbiota of humans and other animals. They have been associated with various infections through their involvement in biofilm formation, modulation of host responses, and interaction with other microorganisms. In this study, two strains previously indicated as Actinomyces spp. were found to be novel members of the genus Schaalia based on their whole genome sequences.

Results

Whole-genome sequencing revealed both strains with a genome size of 2.3 Mbp and GC contents of 65.5%. Phylogenetics analysis for taxonomic placement revealed strains NCTC 9931 and C24 as distinct species within the genus Schaalia. Overall genome-relatedness indices including digital DNA-DNA hybridization (dDDH), and average nucleotide/amino acid identity (ANI/AAI) confirmed both strains as distinct species, with values below the species boundary thresholds (dDDH < 70%, and ANI and AAI < 95%) when compared to nearest type strain Schaalia odontolytica NCTC 9935 T. Pangenome and orthologous analyses highlighted their differences in gene properties and biological functions compared to existing type strains. Additionally, the identification of genomic islands (GIs) and virulence-associated factors indicated their genetic diversity and potential adaptive capabilities, as well as potential implications for human health. Notably, CRISPR-Cas systems in strain NCTC 9931 underscore its adaptive immune mechanisms compared to strain C24.

Conclusions

Based on these findings, strain NCTC 9931T (= ATCC 17982T = DSM 43331T = CIP 104728T = CCUG 18309T = NCTC 14978T = CGMCC 1.90328T) represents a novel species, for which the name Schaalia dentiphila subsp. dentiphila sp. nov. subsp. nov. is proposed, while strain C24T (= NCTC 14980T = CGMCC 1.90329T) represents a distinct novel subspecies, for which the name Schaalia dentiphila subsp. denticola. subsp. nov. is proposed. This study enriches our understanding of the genomic diversity of Schaalia species and paves the way for further investigations into their roles in oral health.

Significance

This research reveals two Schaalia strains, NCTC 9931 T and C24T, as novel entities with distinct genomic features. Expanding the taxonomic framework of the genus Schaalia, this study offers a critical resource for probing the metabolic intricacies and resistance patterns of these bacteria. This work stands as a cornerstone for microbial taxonomy, paving the way for significant advances in clinical diagnostics.
A prospective, randomized, single-blinded study comparing the efficacy and safety of dexmedetomidine and propofol for sedation during endoscopic retrograde cholangiopancreatography
Authors: Zhang Wenyou , Wang Liangrong , Zhu Na , Wu Wenzhi , Liu Haiyan
Published: May 2024

Background

Balanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In various clinical settings, the combination of dexmedetomidine with opioids and benzodiazepines has provided effective sedation with increased safety. The aim of this investigation was to compare the efficacy and safety of dexmedetomidine and propofol for sedation during ERCP.

Methods

Forty-one patients were randomly divided into two groups: the dexmedetomidine (DEX) group and the propofol (PRO) group. Patients in the DEX group received an additional bolus of 0.6 μg kg−1 dexmedetomidine followed by a dexmedetomidine infusion at 1.2 μg kg−1 h−1, whereas the PRO group received 1–2 mg kg−1 of propofol bolus followed by a propofol infusion at 2–3 mg kg−1 h−1. During ERCP, the primary outcome was the incidence of hypoxemia (SpO2 < 90% for > 10 s). Other intraoperative adverse events were also recorded as secondary outcomes, including respiratory depression (respiratory rate of < 10 bpm min−1), hypotension (MAP < 65 mmHg), and bradycardia (HR < 45 beats min−1).

Results

The incidence of hypoxemia was significantly reduced in the DEX group compared to the PRO group (0% versus 28.6%, respectively; P = 0.032). Patients in the PRO group exhibited respiratory depression more frequently than patients in the DEX group (35% versus 81%, respectively; P = 0.003). There were no significant differences in terms of hypotension and bradycardia episodes between groups. During the procedures, the satisfaction scores of endoscopists and patients, as well as the pain and procedure memory scores of patients were comparable between groups.

Conclusion

In comparison with propofol, dexmedetomidine provided adequate sedation safety with no adverse effects on sedation efficacy during ERCP.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2200061468, 25/06/2022.
Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study
Authors: Bes-Berlandier Hugo , Coiffard Benjamin , Bermudez Julien , Demazes-dufeu Nadine , Coltey Bérengère , Boschi Céline , Colson Philippe , Hraiech Sami , Reynaud-Gaubert Martine , Cassir Nadim
Published: May 2024

Background

The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes.

Methods

We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes.

Results

Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047).

Conclusion

The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.
Epidemiological characteristics of asthma-COPD overlap, its association with all-cause mortality, and the mediating role of depressive symptoms: evidence from NHANES 2005–2018
Authors: Zhu Meng , Chen An
Published: May 2024

Background

Asthma-COPD overlap (ACO) is a distinct and intricate respiratory condition that requires specific attention and management. The objective of this cohort study was to examine the epidemiological characteristics of ACO, explore the association between ACO and all-cause mortality, and investigate the potential mediating role of depressive symptoms in this association.

Methods

This retrospective cohort study used data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 and National Death Index (NDI) 2019. A total of 22,745 participants were included: 705 with ACO, 2352 with asthma-only, 853 with COPD-only, and 18,835 without asthma or COPD. The non-ACO group (N = 22,040) referred to the individuals without ACO. Statistical tests were employed to assess differences in some characteristics between the ACO group and the other groups. Cox proportional hazards models were applied to evaluate the relationship between ACO and all-cause mortality, estimating hazard ratios (HR) with 95% confidence intervals. Mediation analysis was conducted to investigate the potential mediating effects of depressive symptoms on the association of ACO with all-cause mortality.

Results

The prevalence of ACO was 3.10% in our study population. Compared to the non-ACO participants, the ACO participants exhibited significantly different characteristics, including higher age, a lower family income-to-poverty ratio, a higher body mass index, higher rates of comorbidities i.e., hypertension, diabetes, hyperlipidemia, cardiovascular disease, and cancer, poorer dietary habits, and a higher rate of depressive disorders. Compared to the participants without ACO, the participants with ACO exhibited a significant increase in all-cause mortality (HR = 1.908, 95%CI 1.578–1.307, p < 0.001). The proportions mediated by depressive symptoms for ACO -associated all-cause mortality were 8.13% (CI: 4.22%-14.00%, p < 0.001).

Conclusions

This study revealed a strong relationship between ACO and all-cause mortality and uncovered a potential psychological mechanism underlying this relationship. Our study indicates the possible necessity of offering comprehensive care to ACO patients, encompassing early detection, lifestyle guidance, and mental health support. Nevertheless, due to the limitations in the study design and the dataset, the results should be interpreted with caution.
Rigid ureteroscopic lithotripsy with a pressure-controlling ureteral access sheath for complex steinstrasse
Authors: Yuming Zhong , Lei Yao , Qiliang Zhai , Xin Huang , Jin Kuang , Song Leming , Xiaolin Deng
Published: May 2024

Objective

To evaluate the safety and efficacy of rigid ureteroscopic lithotripsy with a pressure-controlling ureteral access sheath (PC-UAS) for complex steinstrasse.

Methods

Thirty-one consecutive patients (male: 18; female: 13) with steinstrasse were enrolled, six of whom had concurrent kidney stones. The mean cumulative stone size was 2.7 ± 1.3 cm. The patients were treated with rigid ureteroscopic lithotripsy using a PC-UAS. The cavity pressure parameters were set as follows: control value at -15 mmHg to -2 mmHg, warning value at 20 mmHg, and limit value at 30 mmHg. The infusion flow rate was set at 150–200 ml/min. A holmium laser (550 μm) was used to powderize the stone at 2.0–2.5 J/pulse with a frequency of 20–30 pulses/s. Analyses included cavity pressure, operative time, stone-free rates, and complications.

Results

Among the 31 patients, 29 were successfully treated with PC-UAS, with nine requiring adjunctive flexible ureteroscopy for stone migration to the kidney. Two procedures were converted to percutaneous nephrolithotomies due to failure of sheath placement. The cavity pressure of all 29 patients was well-maintained below 20 mmHg, with clear vision. The mean operative time was 48.2 ± 17.7 min. No complications, such as ureteral perforation, mucosal avulsion, or hemorrhage, occurred. Two cases of Clavien-Dindo grade I complications occurred. No major complications (Clavien-Dindo grade II–V) occurred. The mean postoperative hospitalization time was 1.7 days. The stone-free rates 1 day and 1 month after surgery were 93.1% and 96.6%, respectively. One patient with residual stones underwent extracorporeal shockwaves.

Conclusions

Rigid ureteroscopic lithotripsy with PC-UAS can effectively control the cavity pressure, shorten the operation time, and improve the efficiency of broken stones, thus reducing the complication rate.
Evaluation of rheological properties of soft lining materials with different composition under various temperatures
Authors: Macit Şule Nur , Gürbüz Ayhan , Oyar Perihan
Published: May 2024

Purpose

The aim of this in vitro study was to evaluate the changes the rheological properties of some soft lining materials, to compare the rheological properties and viscoelastic behaviour at different temperatures.

Materials and methods

Five soft lining materials (acrylic and silicone based) were used. the storage modulus (G’), loss modulus (G”), tan delta (tan δ) and complex viscosity (η’) were chosen and for each material, measurements were repeated at 23, 33 and 37  °C, using an oscillating rheometer. All data were statistically analyzed using the Mann Whitney U test, Kruskal Wallis test and Conover’s Multiple Comparison test at the significance level of 0.05.

Results

Soft lining materials had different viscoelastic properties and most of the materials showed different rheological behavior at 23, 33 and 37  °C. At the end of the test (t¹5), at all the temperatures, Sofreliner Tough M had the highest storage modulus values while Visco Gel had the highest loss Tan delta values.

Conclusions

There were significant changes in the rheological parameters of all the materials. Also temperature affected the initial rheological properties, and polymerization reaction of all the materials, depending on temperature increase.

Clinical implications

Temperature affected the initial rheological properties, and polymerization reaction of soft denture liner materials, and clinical inferences should be drawn from such studies conducted. It can be recommended to utilize viscoelastic acrylic-based temporary soft lining materials with lower storage modulus, higher tan delta value, and high viscosity in situations where pain complaint persists and tissue stress is extremely significant, provided that they are replaced often.
Defining a set of teaching EPAs tailored to an undergraduate medical curriculum using a modified Delphi approach
Authors: Peters Harm , Holzhausen Ylva , Czeskleba Anja , Schumann Marwa
Published: May 2024

Background

The concept of entrustable professional activities (EPAs) has recently been extended to operationalize professional tasks in teacher training and faculty development in health professions education. The aim of this study is to report on the process and results of defining a set of teaching EPAs (t-EPAs) tailored to the local characteristics of a particular undergraduate medical program.

Methods

The undergraduate medical program at the Charité – Universitätsmedizin Berlin is competency-based, integrates thematic modules and spans 6 years. A writing team identified teaching EPAs based on the program’s study regulations and drafted content descriptions with titles, specifications and knowledge, skills and attitudes. Content validation involved a modified Delphi procedure with a systematic, iterative interaction between a panel of content experts consisting of purposively selected educators and physicians from our faculty (n = 11) and the writing team. The threshold for a consensus was an agreement of 80% of the participants.

Results

After two Delphi rounds, a consensus was reached regarding the teaching activities to be included and their content descriptions. The response rate was 100% in both Delphi rounds. The Delphi results include the content descriptions of a total of 13 teaching EPAs, organized into the two overarching EPA domains of classroom-based (n = 10) and workplace-based (n = 3) activities. Tailoring the classroom EPAs to small group teaching and the workplace EPAs to supervising medical students led to several distinct EPAs. Another feature was the development of 2 teaching EPAs for interdisciplinary teaching.

Conclusions

In systematic, Delphi-based process, we defined a set of 13 distinct teaching EPAs tailored to a specific undergraduate medical program that cover the core teaching tasks for faculty in this program. Our report on the principles of the process and the results may guide other medical schools and educators in defining and tailoring teaching EPAs according to their contexts.
Reform of the first year of medical studies and diversification of student profiles in France: an unmet need?
Authors: Khanna Raoul K. , Blanchard Emmanuelle , Pasco Jeremy , Diot Patrice , Angoulvant Denis
Published: May 2024

Objectives

To determine whether the reform of the first year of medical studies implemented in September 2020 in France met its objective of diversifying the profiles of students admitted to second year at the faculty of medicine at the University of Tours.

Methods

Single-centered, retrospective study, covering students who passed the first year of medical studies between 2018 and 2022. Student profiles originating from three different entry gateways (PACES, PASS and L.AS) to the second year of medical studies were compared.

Results

One thousand four hundred and seventy-nine students over five promotions were included (806 in PACES, 329 in PASS, 198 in L.AS). The ratio of students who had obtained a baccalaureate with high or highest honors was significantly higher in PACES (85%) and PASS (96%) compared to L.AS (66%; p < 0.001). These differences were related to increased student intake via a standard pass in L.AS (21% compared to 3.2% in PACES and 0.9% in PASS) (p < 0.001). In terms of geographical origin, the proportion of students residing in regions outside the University City area increased significantly in L.AS (11%) compared to PACES (1.7%) and PASS (3.3%) (p < 0.001). The mean number of parents from the white-collar and knowledge professional category was significantly higher in PACES (0.91) and PASS (1.06) compared to L.AS (0.80; p < 0.001).

Conclusion

Students with a scientific background and who obtained highest honors in their high school diploma, remain the standard in PACES and PASS. Diversification of student profiles was achieved only within the L.AS gateway, which represented 42% of total second year admissions during the post-reform year. Student profile diversification was therefore a partially achieved objective and follow up studies of future promotions is needed to assess the medium and long-term impact of the reform. Particular attention should be paid to the future of these students who have different profiles between L.AS and PASS to determine whether these changes will have any impact in the quality of healthcare for the French population.
Barriers to cancer treatment for people experiencing socioeconomic disadvantage in high-income countries: a scoping review
Authors: Bourgeois Amber , Horrill Tara , Mollison Ashley , Stringer Eleah , Lambert Leah K. , Stajduhar Kelli
Published: May 2024

Background

Despite advances in cancer research and treatment, the burden of cancer is not evenly distributed. People experiencing socioeconomic disadvantage have higher rates of cancer, later stage at diagnoses, and are dying of cancers that are preventable and screen-detectable. However, less is known about barriers to accessing cancer treatment.

Methods

We conducted a scoping review of studies examining barriers to accessing cancer treatment for populations experiencing socioeconomic disadvantage in high-income countries, searched across four biomedical databases. Studies published in English between 2008 and 2021 in high-income countries, as defined by the World Bank, and reporting on barriers to cancer treatment were included.

Results

A total of 20 studies were identified. Most (n = 16) reported data from the United States, and the remaining included publications were from Canada (n = 1), Ireland (n = 1), United Kingdom (n = 1), and a scoping review (n = 1). The majority of studies (n = 9) focused on barriers to breast cancer treatment. The most common barriers included: inadequate insurance and financial constraints (n = 16); unstable housing (n = 5); geographical distribution of services and transportation challenges (n = 4); limited resources for social care needs (n = 7); communication challenges (n = 9); system disintegration (n = 5); implicit bias (n = 4); advanced diagnosis and comorbidities (n = 8); psychosocial dimensions and contexts (n = 6); and limited social support networks (n = 3). The compounding effect of multiple barriers exacerbated poor access to cancer treatment, with relevance across many social locations.

Conclusion

This review highlights barriers to cancer treatment across multiple levels, and underscores the importance of identifying patients at risk for socioeconomic disadvantage to improve access to treatment and cancer outcomes. Findings provide an understanding of barriers that can inform future, equity-oriented policy, practice, and service innovation.
Single-base resolution quantitative genome methylation analysis in the model bacterium Helicobacter pylori by enzymatic methyl sequencing (EM-Seq) reveals influence of strain, growth phase, and methyl homeostasis
Authors: Patel Lubna , Ailloud Florent , Suerbaum Sebastian , Josenhans Christine
Published: May 2024

Background

Bacterial epigenetics is a rapidly expanding research field. DNA methylation by diverse bacterial methyltransferases (MTases) contributes to genomic integrity and replication, and many recent studies extended MTase function also to global transcript regulation and phenotypic variation. Helicobacter pylori is currently one of those bacterial species which possess the highest number and the most variably expressed set of DNA MTases. Next-generation sequencing technologies can directly detect DNA base methylation. However, they still have limitations in their quantitative and qualitative performance, in particular for cytosine methylation.

Results

As a complementing approach, we used enzymatic methyl sequencing (EM-Seq), a technology recently established that has not yet been fully evaluated for bacteria. Thereby, we assessed quantitatively, at single-base resolution, whole genome cytosine methylation for all methylated cytosine motifs in two different H. pylori strains and isogenic MTase mutants. EM-Seq reliably detected both m5C and m4C methylation. We demonstrated that three different active cytosine MTases in H. pylori provide considerably different levels of average genome-wide single-base methylation, in contrast to isogenic mutants which completely lost specific motif methylation. We found that strain identity and changed environmental conditions, such as growth phase and interference with methyl donor homeostasis, significantly influenced quantitative global and local genome-wide methylation in H. pylori at specific motifs. We also identified significantly hyper- or hypo-methylated cytosines, partially linked to overlapping MTase target motifs. Notably, we revealed differentially methylated cytosines in genome-wide coding regions under conditions of methionine depletion, which can be linked to transcript regulation.

Conclusions

This study offers new knowledge on H. pylori global and local genome-wide methylation and establishes EM-Seq for quantitative single-site resolution analyses of bacterial cytosine methylation.
Associations between vaping and self-reported respiratory symptoms in young people in Canada, England and the US
Authors: Brose Leonie S. , Reid Jessica L. , Robson Debbie , McNeill Ann , Hammond David
Published: May 2024

Background

Prevalence of youth nicotine vaping has increased, heightening concerns around negative health effects. This study aimed to compare self-reported respiratory symptoms among youth by vaping behaviours.

Methods

Participants (n = 39,214) aged 16–19 from the 2020 and 2021 International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Surveys (Canada, England, US). Weighted multivariable logistic regression assessed associations between reporting any of five respiratory symptoms in the past week (shortness of breath, wheezing, chest pain, phlegm, cough) and: past 30-day smoking and/or vaping; lifetime/current vaping. Among past-30-day vapers (n = 4644), we assessed associations between symptoms and vaping frequency, use of nicotine salts, usual flavour and device type(s).

Results

Overall, 27.8% reported experiencing any of the five respiratory symptoms. Compared with youth who had only vaped, those who had only smoked had similar odds of symptoms [adjusted odds ratio, OR (95% confidence interval, CI): 0.97 (0.85–1.10)], those who both smoked and vaped had higher odds [1.26 (1.12–1.42)], and those who had done neither, lower odds [0.67 (0.61–0.72)]. Compared with those who had never vaped, past use, experimentation and current regular or occasional use were all associated with higher odds. Reporting usually using nicotine salts was associated with higher odds of symptoms [1.43 (1.22–1.68)] than non-salt but was often uncertain. Compared with tobacco flavour (including with menthol), menthol/mint and sweets flavours were associated with similar odds; fruit [1.44 (1.07–1.93)], multiple [1.76 (1.30–2.39)] and ‘other’ [2.14 (1.45–3.16)] flavours with higher odds. All device types were associated with similar odds.

Conclusions

Among youth, vaping was associated with increased reporting of past-week respiratory symptoms. Among those who vaped, some flavour types and potentially nicotine salts were associated with respiratory symptoms.
USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase
Authors: Chen Yunshang , Feng Xue , Wu Zilong , Yang Yongqiang , Rao Xinrui , Meng Rui , Zhang Sheng , Dong Xiaorong , Xu Shuangbing , Wu Gang , Jie Xiaohua
Published: May 2024

Background

Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment.

Methods

The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1.

Results

Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism.

Conclusion

USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.
Assessing the efficiency and microbial diversity of H2S-removing biotrickling filters at various pH conditions
Authors: Rouhollahi Abbas Abbas , Giyahchi Minoo , Dastgheib Seyed Mohammad Mehdi , Moghimi Hamid
Published: May 2024

This study aimed to investigate the operation of three parallel biotrickling filters (BTFs) in removing H2S at different pH conditions (haloalkaliphilic, neutrophilic, and acidophilic) and their associated microbial population in the biodesulfurization process. BTF columns were inoculated with enriched inoculum and experiments were performed by gradually reducing Empty Bed Retention Time (EBRT) and increasing inlet concentration in which the maximum removal efficiency and maximum elimination capacity in EBRT 60 s reached their maximum level in haloalkaline condition (91% and 179.5 g S-H2S m−3 h−1). For visualizing the attached microbial biofilms on pall rings, Scanning Electron Microscopy (SEM) was used and microbial community structure analysis by NGS showed that the most abundant phyla in haBTF, nBTF, and aBTF belong to Gammaproteobacteria, Betaproteobacteria, and Acidithiobacillia, respectively. Shannon and Simpson indexes evaluation showed a lower diversity of bacteria in the aBTF reactor than that of nBTF and haBTF and beta analysis indicated a different composition of bacteria in haBTF compared to the other two filters. These results indicated that the proper performance of BTF under haloalkaliphilic conditions is the most effective way for H2S removal from air pollutants of different industries.

Graphical Abstract
LncRNA PART1 promotes malignant biological behaviours associated with head and neck cancer cells via synergistic action with FUT6
Authors: Yao Yanheng , Zhang Yuxin , Shi Jiyuan , Xu Xiling , Gao Yunran , Bai Suwen , Hu Qin , Wu Jing , Du Juan
Published: May 2024

The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.