bluuebunny/crossref_metadata_2025 huggingface dataset:
Verse and Conversion
Authors: Ungvary David
Published: July 2024

This chapter explores a question central to the development of Christian Latin poetry: Was there a way for classically trained authors to accommodate pagan literary traditions within a rigorous Christian life? Inquiry begins with the case of a young poet and member of Augustine’s retinue named Licentius, who, in Augustine’s De ordine, is prompted to consider whether there is room for verse writing within Christian life. Licentius’s subsequent conversion illustrates the ethical negotiations that Roman authors faced in balancing classical literary interests against the demands of an increasingly ascetic Christianity. This chapter argues that, to better appreciate Licentius’s dilemma, students of Late Latin verse must nuance their understandings of the literary dynamics of conversion, Christianization, asceticism, and religious identification. Subsections demonstrate the book’s interest in and methods for capturing particularly integrative forms of asceticism, which fostered the co-existence of classical and Christian attitudes and practices. Poetic expressions of asceticism are explored through the writings of Paulinus of Nola, dispatched by Augustine to teach Licentius about the possibilities of Christian poetry. Paulinus’s poetic tactics provided ambivalent Christians like Licentius with a model for converting poetry to Christian spiritual use.
Verse and Incursion
Authors: Ungvary David
Published: July 2024

This chapter examines how Gallo-Roman Christian poetry became a discourse of religious reform in the aftermath of civil war and barbarian invasion. Amid these crises, regional Christian poets composed poems to reflect on the spiritual consequences of political destabilization, and to direct compatriots to reorder their worlds according to Christian systems of value and ethics. At the center of the chapter is a close reading of the first of these poems of reform, the Epigramma Paulini, which responds to the barbarian breach of the Rhine in 406/7 with a diagnosis of Gaul’s moral and religious condition. Interpretation of the poem connects its allegorical, metapoetic, and genre-bending features to the conflicts of identity and ideology that aristocratic readers faced under the pressures of Christianization and barbarian invasion. The chapter concludes by examining evidence for conversation between Gallo-Roman ascetic authors and outside religious experts like Jerome, who asserted themselves as authoritative spiritual interpreters of Gaul’s political crises. Analysis suggests that interventions like Jerome’s propelled Gallo-Roman writers to develop their own idioms of spiritual reform to help reclaim a sense of religious self-determination.
Epilogue
Authors: Ungvary David
Published: July 2024

This chapter points to texts and contexts beyond Gaul where scholars may extend future explorations of the interplay between classicizing Latin poetry and Christian asceticism. Discussion centers on Ennodius of Pavia’s Eucharisticon, a confessional prose text written by a renunciant poet-cleric in Ostrogothic Italy. Interpretation seeks to explain the peculiarities of Ennodius’s self-presentation and pointed disavowal of poetry in light of the study’s previous readings. Allusive reverence toward Augustine’s Confessions, social and familial connections to authors like Sidonius and Avitus, and ascetically informed language within Ennodius’s text all reveal intellectual and literary affinities with Gallo-Roman Christian poetry developed through the fifth century. The study concludes by suggesting ways of deepening critical appreciation of the transmission and evolution of ascetic theories and practices of poetry into the early medieval period. It thus invites and equips readers to revisit the force of Christian Latin poetics in shaping the strategies and practices of conversion, authorship, and Christianization that gave form to the emergent cultures of the post-Roman West.
Shared patterns of glial transcriptional dysregulation link Huntington’s disease and schizophrenia
Authors: Huynh Nguyen P T , Osipovitch Mikhail , Foti Rossana , Bates Janna , Mansky Benjamin , Cano Jose C , Benraiss Abdellatif , Zhao Chuntao , Lu Q Richard , Goldman Steven A
Published: July 2024

Huntington’s disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction and hypomyelination. To assess whether a common mechanism might underlie the similar glial pathology of these otherwise disparate conditions, we used comparative correlation network approaches to analyse RNA-sequencing data from human glial progenitor cells (hGPCs) produced from disease-derived pluripotent stem cells.

We identified gene sets preserved between Huntington’s disease and schizophrenia hGPCs yet distinct from normal controls that included 174 highly connected genes in the shared disease-associated network, focusing on genes involved in synaptic signalling. These synaptic genes were largely suppressed in both schizophrenia and Huntington’s disease hGPCs, and gene regulatory network analysis identified a core set of upstream regulators of this network, of which OLIG2 and TCF7L2 were prominent. Among their downstream targets, ADGRL3, a modulator of glutamatergic synapses, was notably suppressed in both schizophrenia and Huntington’s disease hGPCs. Chromatin immunoprecipitation sequencing confirmed that OLIG2 and TCF7L2 each bound to the regulatory region of ADGRL3, whose expression was then rescued by lentiviral overexpression of these transcription factors.

These data suggest that the disease-associated suppression of OLIG2 and TCF7L2-dependent transcription of glutamate signalling regulators may impair glial receptivity to neuronal glutamate. The consequent loss of activity-dependent mobilization of hGPCs may yield deficient oligodendrocyte production, and hence the hypomyelination noted in these disorders, as well as the disrupted astrocytic differentiation and attendant synaptic dysfunction associated with each. Together, these data highlight the importance of convergent glial molecular pathology in both the pathogenesis and phenotypic similarities of two otherwise unrelated disorders, Huntington’s disease and schizophrenia.
Scenario of solar energy and policies in India
Authors: Kumar M Sathish , Kumari Prity , Lad Y A , Maria Sherin
Published: July 2024

Solar power is energy from the Sun that is converted into thermal or electrical energy. China, the USA, and India have the world’s richest solar energy sources. India receives solar radiation with an average intensity of 200 MW/km2 and 250–300 sunny days a year. The solar radiation in India varies from 4 to 7 kWh/m2/day, with 2300–3200 sunshine hours yearly, depending on the region. Badhla Solar Park, Jodhpur, India, is the world’s largest solar plant, with 2.25 GW of installed capacity. Solar energy is the best alternative electricity source used explicitly in the agricultural sector. In the farming sector, the consumption of solar energy has been increasing. The major issues were the installation costs, low availability of technicians, and poor quality of panels. The focus on skill development equips the workforce to drive innovation, efficiency, and sustained growth in the renewable-energy field. With the support of international collaboration and a skilled workforce, India’s progress in solar energy development is a boon for the industry.
Genetic testing in early-onset atrial fibrillation
Authors: Kany Shinwan , Jurgens Sean J , Rämö Joel T , Christophersen Ingrid E , Rienstra Michiel , Chung Mina K , Olesen Morten S , Ackerman Michael J , McNally Elizabeth M , Semsarian Christopher , Schnabel Renate B , Wilde Arthur A M , Benjamin Emelia J , Rehm Heidi L , Kirchhof Paulus , Bezzina Connie R , Roden Dan M , Shoemaker M Benjamin , Ellinor Patrick T
Published: July 2024

Atrial fibrillation (AF) is a globally prevalent cardiac arrhythmia with significant genetic underpinnings, as highlighted by recent large-scale genetic studies. A prominent clinical and genetic overlap exists between AF, heritable ventricular cardiomyopathies, and arrhythmia syndromes, underlining the potential of AF as an early indicator of severe ventricular disease in younger individuals. Indeed, several recent studies have demonstrated meaningful yields of rare pathogenic variants among early-onset AF patients (∼4%–11%), most notably for cardiomyopathy genes in which rare variants are considered clinically actionable. Genetic testing thus presents a promising opportunity to identify monogenetic defects linked to AF and inherited cardiac conditions, such as cardiomyopathy, and may contribute to prognosis and management in early-onset AF patients. A first step towards recognizing this monogenic contribution was taken with the Class IIb recommendation for genetic testing in AF patients aged 45 years or younger by the 2023 American College of Cardiology/American Heart Association guidelines for AF. By identifying pathogenic genetic variants known to underlie inherited cardiomyopathies and arrhythmia syndromes, a personalized care pathway can be developed, encompassing more tailored screening, cascade testing, and potentially genotype-informed prognosis and preventive measures. However, this can only be ensured by frameworks that are developed and supported by all stakeholders. Ambiguity in test results such as variants of uncertain significance remain a major challenge and as many as ∼60% of people with early-onset AF might carry such variants. Patient education (including pretest counselling), training of genetic teams, selection of high-confidence genes, and careful reporting are strategies to mitigate this. Further challenges to implementation include financial barriers, insurability issues, workforce limitations, and the need for standardized definitions in a fast-moving field. Moreover, the prevailing genetic evidence largely rests on European descent populations, underscoring the need for diverse research cohorts and international collaboration. Embracing these challenges and the potential of genetic testing may improve AF care. However, further research—mechanistic, translational, and clinical—is urgently needed.
Low CD4 counts predict excessive weight gains during first-line treatment for HIV
Authors: Hill Andrew , Tovar Sanchez Tamara , Delaporte Eric , Sokhela Simiso , Simmons Bryony , Kouanfack Charles , Mccann Kaitlyn , Levi Jacob , Fairhead Cassandra , Venter Francois
Published: July 2024

Background

Weight gain is common after antiretroviral initiation, especially among females, those of black race and lower baseline CD4, although this may potentially be due to lower baseline weight. Use of tenofovir disoproxil fumarate or efavirenz can suppress weight gain.

Methods

Data were pooled from the ADVANCE (n = 1053), NAMSAL (n = 613) and WHRI001 (n = 536) trials investigating first-line regimen. Week 96 weight and body mass index (BMI) was stratified by baseline CD4. Multivariable models of weight change and incident obesity (BMI ≥30 kg/m2) were adjusted for baseline CD4, age, sex, tenofovir disoproxil fumarate, efavirenz, baseline BMI and trial.

Results

Participants across all treatment arms experienced weight gain from baseline to week 96, with baseline CD4 count, baseline HIV RNA, tenofovir alafenamide and dolutegravir use, and female sex significant predictors. Mean unadjusted weight change was highest with CD4 < 100 (+8.6 kg; SD = 8.2) and lowest with CD4 ≥ 350 (+3.0 kg; SD = 6.5). This weight gain in CD4 < 100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4 < 100 group. Although not statistically significant, obesity rate (BMI ≥ 30 kg/m2) in those taking TAF/FTC + DTG with CD4 < 100 overtook that seen in CD4 ≥ 350, despite lower baseline obesity prevalence. The unadjusted findings were corroborated in multivariable longitudinal models.

Conclusions

Participants with low CD4 may demonstrate significant ‘overshoot’ weight gain, in addition to ‘return to health’, with a trend towards increased risk of obesity when initiated on TAF/FTC + DTG. Use of tenofovir disoproxil fumarate and efavirenz were associated with smaller weight gains. Effective weight management strategies are needed, especially for individuals with low baseline CD4.
(360) WHICH OF PDE5 INHIBITORS IS MOST EFFECTIVE IN THE TREATMENT OF ERECTILE DYSFUNCTION IN PATIENTS WITH SPINAL CORD INJURY? A NETWORK META-ANALYSIS
Authors: Tienforti Dr Daniele , Castellini Chiara , Barbonetti Prof Arcangelo
Published: July 2024

Objectives

PDE5 inhibitors (PDE5i) represent the first-line drugs in the treatment of spinal cord injury (SCI)-related erectile dysfunction (ED). Available molecules have differences that should guide personalization of treatment. We compared the efficacy of PDE5 inhibitors to define which is more effective in treating SCI-related ED.

Methods

A systematic search was performed. A traditional pairwise meta-analyses were conducted including only studies in which PDE5i were directly compared with placebo, then a network meta-analysis (NMA) was conducted. Based on the assumption of transitivity, if two treatments, A and B, have never been compared with each other but both have been compared with a third treatment (e.g., a placebo), the NMA can provide information on the A vs. B comparison by means of the statistical method of “indirect comparison”. With this approach, multiple treatments are compared within a single statistical model generating an efficacy hierarchy to drive clinical practice.

Results

The search identified 10 trials. The most common comparison was between sildenafil and placebo. All three molecules were compared at least once with each other and with placebo. The results of the NMA confirmed a significant improvement in erectile function with each of the three molecules. At the comparative analysis, tadalafil, which was 5 times more effective than placebo, was associated with the highest surface under the cumulative ranking curve (SUCRA) value (0.81), thus proving to be the best PDE5i in the treatment of SCI-related ED, followed by vardenafil (0.68) and sildenafil (0.49) (Figure 1).

Conclusions

In men with SCI who are candidates for PDE5i treatment for ED, the clinician's choice should fall on tadalafil, leaving vardenafil and sildenafil as second-line choices. Further head-to-head comparison studies will be needed to confirm these results and to identify most useful clinical and neurological features for selecting patients who are candidates for prescription of the different molecules.

Conflicts of Interest

The authors have no conflicts of interest to declare.
Revisiting the dead time effects of Insight-HXMT/ME on timing analysis
Authors: Tuo Youli , Li Xiaobo , Tan Ying , Wu Baiyang , Jiang Weichun , Song Liming , Qu Jinlu , Gogate Sudeep , Zhang Shuang-Nan , Santangelo Andrea
Published: July 2024

Dead time is a common instrumental effect of X-ray detectors, which would alter the behaviour of timing properties of astronomical signals, such as distorting the shape of power density spectra (PDS), affecting the root-mean-square of potential quasi-periodic oscillation signals, etc. We revisit the effects of the dead time of Medium Energy X-ray telescope (ME) onboard Insight-HXMT based on the simulation of electronic read-out mechanism that causes the dead time and the real data. We investigate dead time effects on the pulse profile as well as the quasi–periodic oscillation (QPO) signals. The dead time coefficient suggests a linear correlation with the observed count rate in each phase bin of the pulse profile according to the simulation of periodic signal as well as the real data observed on Swift J0243.6+6124. The Fourier-amplitude-difference (FAD) method could well recover the intrinsic shape of the observed PDS in the case that the PDS is from two identical detectors. We apply this technique on ME, by splitting the nine FPGA modules into two groups. The results indicate that the FAD technique suits the case when two groups of detectors are not largely different; and the recovered PDS of Sco X-1 observed by ME slightly enhances the significance of the previously known QPO signal, meanwhile the root-mean-square of QPO is significantly improved. We provide the FAD correction tool implemented in HXMTDAS for users in the future to better analyse QPO signals.
Epidural Blood Patch for the Treatment of Spontaneous Intracranial Hypotension: A Case Series
Authors: Gomez Maria , Sharma Manas , Chan Tommy Lik Hang , Bellingham Geoff , Chui Jason
Published: July 2024

Background:

Epidural blood patch (EBP) is frequently used for the treatment of spontaneous intracranial hypotension (SIH) and anesthesiologists are often involved in performing such procedures. However, the optimal technique and approach of EBP remains uncertain.

Methods:

This case series included adult patients with SIH who underwent EBPs at London Health Science Centre, Ontario, Canada between 2010 and 2022. Demographics, clinical presentations, investigations, and EBP treatment details were collected and analyzed. Univariate analysis was used to investigate the association of the variables with the likelihood of EBP 1-month efficacy and the efficacy duration of EBP.

Results:

The study included 36 patients with SIH who received at least 1 EBP. EBPs provided immediate relief in almost all patients, albeit with diminishing effects over time. The 1-month efficacy improved with increasing number of EBP attempts (P=0.032, Fisher exact test), though no particular EBP technique or volume of injectate was associated with better efficacy (P=0.38, Fisher exact test). Though permanent resolution of symptoms was observed in only 24 of 82 EBPs (29%), 24 of 36 patients (67%) had permanent symptom resolution following repeated EBPs.

Conclusions:

EBP is a promising treatment and symptomatic relief option in patients suffering from the debilitating symptoms of SIH. Tailored EBP techniques, including use of targeted higher volume EBP and a multi-level catheter guided technique for refractory cases, showed efficacy in our institutional setting. Despite its limitations, this study contributes valuable insights and experiences into the use of EBP for treatment of SIH.
Development and Validation of a Machine Learning COVID-19 Veteran (COVet) Deterioration Risk Score
Authors: Govindan Sushant , Spicer Alexandra , Bearce Matthew , Schaefer Richard S. , Uhl Andrea , Alterovitz Gil , Kim Michael J. , Carey Kyle A. , Shah Nirav S. , Winslow Christopher , Gilbert Emily , Stey Anne , Weiss Alan M. , Amin Devendra , Karway George , Martin Jennie , Edelson Dana P. , Churpek Matthew M.
Published: July 2024

BACKGROUND AND OBJECTIVE:

To develop the COVid Veteran (COVet) score for clinical deterioration in Veterans hospitalized with COVID-19 and further validate this model in both Veteran and non-Veteran samples. No such score has been derived and validated while incorporating a Veteran sample.

DERIVATION COHORT:

Adults (age ≥ 18 yr) hospitalized outside the ICU with a diagnosis of COVID-19 for model development to the Veterans Health Administration (VHA) (n = 80 hospitals).

VALIDATION COHORT:

External validation occurred in a VHA cohort of 34 hospitals, as well as six non-Veteran health systems for further external validation (n = 21 hospitals) between 2020 and 2023.

PREDICTION MODEL:

eXtreme Gradient Boosting machine learning methods were used, and performance was assessed using the area under the receiver operating characteristic curve and compared with the National Early Warning Score (NEWS). The primary outcome was transfer to the ICU or death within 24 hours of each new variable observation. Model predictor variables included demographics, vital signs, structured flowsheet data, and laboratory values.

RESULTS:

A total of 96,908 admissions occurred during the study period, of which 59,897 were in the Veteran sample and 37,011 were in the non-Veteran sample. During external validation in the Veteran sample, the model demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.88. This was significantly higher than NEWS (0.79; p < 0.01). In the non-Veteran sample, the model also demonstrated excellent discrimination (0.86 vs. 0.79 for NEWS; p < 0.01). The top three variables of importance were eosinophil percentage, mean oxygen saturation in the prior 24-hour period, and worst mental status in the prior 24-hour period.

CONCLUSIONS:

We used machine learning methods to develop and validate a highly accurate early warning score in both Veterans and non-Veterans hospitalized with COVID-19. The model could lead to earlier identification and therapy, which may improve outcomes.
Severe acute respiratory syndrome coronavirus 2-specific T-cell responses are induced in people living with human immunodeficiency virus after booster vaccination
Authors: Wang Xiuwen , Li Yongzheng , Jin Junyan , Chai Xiaoran , Ma Zhenglai , Duan Junyi , Zhang Guanghui , Huang Tao , Zhang Xin , Zhang Tong , Wu Hao , Cao Yunlong , Su Bin
Published: July 2024

Background:

T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.

Methods:

Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.

Results:

The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4+ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8+ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8+ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F.

Conclusions:

Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.
Necrotizing Fasciitis of the Hand: Management with Literature Review
Authors: Delavari Sarina , Megas Ioannis-Fivos , Billner Moritz , Reichert Bert , Breidung David
Published: July 2024

This report presents a case of necrotizing fasciitis following a seemingly minor injury sustained from handling a spiny plant. Despite initial primary care by a physician, the patient presented with severe septic shock and necrotizing fasciitis of the hand, necessitating emergency surgical intervention. The use of scoring systems aided in the prompt recognition of the condition. Subsequent surgery was required due to infection progression, leading to significant soft tissue defects and functional impairment. The patient underwent multiple reconstructive procedures, including placement of dermis-replacement material and, ultimately, free flap reconstruction, to restore the hand function. This case report highlights the importance of rapid identification of potential cases of necrotizing fasciitis in cases of hand infections, demonstrates that scoring systems can assist in smaller affected body sites such as the hand, and illustrates the difficulties of defect reconstruction following necrotizing fasciitis.
PGD2/DP1 axis promotes liver regeneration by secreting Wnt2 in KCs in mice
Authors: Li Juanjuan , Zheng Yinghong , Duan Zhenzhen , Zeng Qingye , Qu Jin , Zhang Jincheng , Liu Jiao , Shang Wenlong , Tao Xixi , Yu Tingting , Li Xinzhi , Wang Lifu , Yang Liming , Kong Deping , Yu Ying
Published: July 2024

Background and Aims:

The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin D2, a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of prostaglandin D2 in the injury-induced liver regeneration remains unclear.

Approach and Results:

Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic prostaglandin D2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67+ hepatocyte proliferation, and G2/M phase hepatocytes. In addition, DP1 deficiency, specifically in resident KCs, and not in endothelial cells or HSCs, retarded liver regeneration in mice after PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/β-catenin signaling. Adeno-associated virus vector serotype 8–mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice after PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice.

Conclusions:

DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2 and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.
Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis
Authors: Koh Benjamin , Xiao Jieling , Ng Cheng Han , Law Michelle , Gunalan Shyna Zhuoying , Danpanichkul Pojsakorn , Ramadoss Vijay , Sim Benedix Kuan Loon , Tan En Ying , Teo Chong Boon , Nah Benjamin , Teng Margaret , Wijarnpreecha Karn , Seko Yuya , Lim Mei Chin , Takahashi Hirokazu , Nakajima Atsushi , Noureddin Mazen , Muthiah Mark , Huang Daniel Q. , Loomba Rohit
Published: July 2024

Background and Aims:

Metabolic dysfunction–associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in MRI proton-density-fat fraction (PDFF) are associated with MASH resolution. We aimed to determine the relative efficacy of therapeutic agents for reducing hepatic fat, assessed by MRI-PDFF.

Approach and Results:

In this systematic review and network meta-analysis, we searched MEDLINE and Embase from inception until December 26, 2023, for published randomized controlled trials comparing pharmacological interventions in patients with MASH that assessed changes in MRI-PDFF. The primary outcome was the absolute change in MRI-PDFF. The secondary outcome was a ≥30% decline in MRI-PDFF. A surface under-the-curve cumulative ranking probabilities (SUCRA) analysis was performed. Of 1550 records, a total of 39 randomized controlled trials (3311 participants) met the inclusion criteria. For MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were ranked the most effective interventions. At 24 weeks, efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were ranked the most effective interventions for achieving a ≥30% decline in MRI-PDFF.

Conclusions:

This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat. These data may help inform the design and sample size calculation of future clinical trials and assist in the selection of combination therapy.
Expert Consensus on the Prevention and Treatment of Chronic Hepatitis B in Children
Authors:   Chinese Society of Infectious Diseases, Chinese Medical Association,   Chinese Society of Hepatology, Chinese Medical Association,   Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association,   National Clinical Research Center for Infectious Diseases (Beijing)
Published: July 2024

The aim of this consensus is to standardize the prevention, diagnosis, and treatment of chronic hepatitis B in children and to achieve the goal of “eliminating viral hepatitis as a major public health threat by 2030” issued by the World Health Organization. Formulated by organized experts of the Chinese Society of Infectious Diseases and Chinese Society of Hepatology, Chinese Medical Association; Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association; and the National Clinical Research Center for Infectious Diseases (Beijing), the consensus provides the latest evidence and recommendations for the prevention, diagnosis, and treatment of chronic hepatitis B in children.
The Effectiveness of a Human Trafficking Protocol in the Emergency Department
Authors: Bastien Danielle Jordan , Peters Rosalind M.
Published: July 2024

Background:

Human trafficking affects nearly 1.1 million persons in the United States. Over 50% of victims will receive care in an emergency department (ED) during their exploitation.

Purpose:

The purpose of this study was to assess the effectiveness of a human trafficking protocol and electronic medical record screening and assessment tool in identifying victims of human trafficking in the ED.

Methods:

A 5-year, retrospective chart audit was conducted.

Results:

Over 2 million ED visits occurred during the 5-year study period. Less than 1% (n = 525) of those patients screened positive as potential victims, while 45 (8.6%) were confirmed trafficking victims. The number of victims identified dropped following the pandemic.

Conclusions:

Pandemic issues, staffing turnover, and lack of ongoing trafficking education impeded the identification of victims. Recommended changes to the protocol are presented.
Explantation with Lateral Pedicle Mastopexy
Authors: Macmillan R. Douglas , Bell Kara , Wilson Emma , Asgeirsson Kristjan S.
Published: July 2024

Background:

Although breast explantation combined with mastopexy is an increasingly common procedure, it does present certain technical difficulties. The authors present a technique of explantation mastopexy with the use of an extended lateral pedicle for autoaugmentation.

Methods:

A consecutive series of 40 cases was reviewed retrospectively, with a patient-reported outcome questionnaire and photography at 3 and 12 months.

Results:

The mean patient age was 57 years (range, 40 to 70 years), and the mean duration of implantation was 20.4 years (range, 7 to 42 years). Twelve women had undergone previous mastopexy (30%). Minor wound complications requiring simple dressings were seen in 7 patients (17.5%). Major infected wound problems occurred in 1 patient, who was a smoker and had other comorbidities. All except 1 patient reported being satisfied or very satisfied with the outcome, with a mean patient-reported satisfaction score of 4.9 of 5. When the photographs were independently assessed by a cosmetic practitioner, all patients were rated as average, good, or very good, with a mean score of 4.1 of 5.

Conclusions:

The procedure is associated with low risk of postoperative complications, good cosmetic outcomes, and a high degree of patient satisfaction. The authors believe this technique provides a logical, reproducible method for combined explantation and mastopexy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Mastoid Fascia Tissue Graft as a Tip Camouflage Technique in Rhinoplasty: A Reliable Alternative to Soft Cartilage Grafts
Authors: Tugertimur Buğra , Datta Shaishav , Goote Paige , Hanna Steven A. , Morris Matthew , Mattos David , Reish Richard G.
Published: July 2024

Background:

Traditional rhinoplasty tip grafts often lead to visibility issues, prompting patients to seek revision surgery. The mastoid fascia tissue graft (MFTG) provides a natural-appearing alternative with an acceptable risk of complication. The MFTG remains less visible through the skin and helps camouflage and conceal tip irregularities. This study of 193 patients examines the MFTG’s effectiveness in nasal tip refinement, evaluating revision and infection rates.

Methods:

A retrospective analysis of MFTG use for nasal tip appearance during open rhinoplasty in the senior author’s (R.G.R.) practice was conducted, covering the period from January of 2019 to June of 2022. Inclusion criteria encompassed open rhinoplasty cases using mastoid tissue for tip appearance with at least 12 months of follow-up. Among 2003 cases, 193 met these criteria and were evaluated for subsequent revision and infection rates.

Results:

The average patient age was 34.2 years (175 female patients and 18 male patients). Primary rhinoplasty was performed in 113 patients, with 80 receiving revision operations. The average follow-up was 14.8 months. Six patients (3.1%) overall needed extended antibiotics, including 1 primary rhinoplasty patient (0.9%) and 5 secondary rhinoplasty patients (6.3%). Overall, revision rhinoplasty was required in 6 patients (3.1%) (1 primary patient [0.9%] and 5 secondary rhinoplasty patients [6.3%]).

Conclusions:

MFTG use for an aesthetically pleasing nasal tip appearance is a safe, convenient, and effective technique for camouflaging and concealing nasal tip contour irregularities in both primary and revision rhinoplasty. Use of the MTFG is associated with minimal morbidity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The state of play of rodent models for the study of Clostridioides difficile infection
Authors: Brosse Anaïs , Coullon Héloïse , Janoir Claire , Péchiné Séverine
Published: July 2024

Clostridioides difficile is the most common cause of nosocomial antibiotic-associated diarrhoea and is responsible for a spectrum of diseases characterized by high levels of recurrence and morbidity. In some cases, complications can lead to death. Currently, several types of animal models have been developed to study various aspects of C. difficile infection (CDI), such as colonization, virulence, transmission and recurrence. These models have also been used to test the role of environmental conditions, such as diet, age and microbiome that modulate infection outcome, and to evaluate several therapeutic strategies. Different rodent models have been used successfully, such as the hamster model and the gnotobiotic and conventional mouse models. These models can be applied to study either the initial CDI infectious process or recurrences. The applications of existing rodent models and their advantages and disadvantages are discussed here.
Synoviocytes assist in modulating the effect of Ross River virus infection in micromass-cultured primary human chondrocytes
Authors: Freppel Wesley , Lim Elisa X.Y. , Rudd Penny A. , Herrero Lara J.
Published: July 2024

Graphical abstract

A schematic representation of the study methodology. Human micromass-cultured chondrocytes were either directly infected with RRV or secondarily through co-culture with RRV-infected FLS. Micromass chondrocytes were analysed after 1, 3 and 5 days post-infection for gene expression using a PCR array and for viral load using genome copy number qPCR. FLS were analysed for viral load via qPCR, and supernatants were analysed for infectious viral particles using a plaque assay.
Relationship between consumer behavior, perception of nutritional
information, and menu factors on fast food using eye-tracking: A study on
university students in Jeonju
Authors: Min Kyungjong , Lee Kunjong , Chung Heajung
Published: July 2024

This study analyzed the factors that influence menu choices through eye-tracking
and questionnaires in menu design. Demographic data of subjects coincided with
choosing a menu and eye-tracking data. Hot Crispy Chicken Burger is the most
popular menu. The study found that regardless of the selected menu, the menu
name (35.5 seconds), price (21.6 seconds), and image (16.0 seconds) were viewed
the longest, followed by country of origin (8.81 seconds), calories (4.6
seconds), and special indications (p<0.05). The menu name and image were
checked more frequently, while calorie information was checked less often. As a
result of analyzing various factors that influence menu selection through,
Consumer experience and image greatly influenced menu choices. Therefore, if you
want to receive a menu selection, it is considered effective to make good use of
the menu name and image. In results of principal component analysis (PCA) by
gender showed. Men had the longest price in the fixation duration. But, for
females, there was a significant difference in gaze fixation when they took the
exam, with menu names and special indications being important selection
criteria. Since the results show that selection criteria and information
acquisition methods differ depending on gender, this research is thought to be
able to suggest directions for menu design.
Inter-individual variability in motor learning due to differences in effective learning rates between generalist and specialist memory stores
Authors: Osu Rieko , Sugimoto Norikazu , Yoshioka Toshinori , Schweighofer Nicolas , Kawato Mitsuo
Published: July 2024

Humans exhibit large interindividual differences in motor learning ability. However, most previous studies have examined properties common across populations, with less emphasis on interindividual differences. We hypothesized here, based on our previous experimental and computational motor adaptation studies, that individual differences in effective learning rates between a generalist memory module that assumes environmental continuity and specialist modules that are responsive to trial-by-trial environmental changes could explain both large population-wise and individual-wise differences in dual tasks adaptation under block and random schedules. Participants adapted to two opposing force fields, either sequentially with alternating training blocks or simultaneously with random sequences. As previously reported, in the block training schedule, all participants adapted to the force field presented in a block but showed large interference in the subsequent opposing force field blocks, such that adapting to the two force fields was impossible. In contrast, in the random training schedule, participants could adapt to the two conflicting tasks simultaneously as a group; however, large interindividual variability was observed. A modified MOSAIC computational model of motor learning equipped with one generalist module and two specialist modules explained the observed behavior and variability for wide parameter ranges: when the predictions errors were large and consistent as in block schedules, the generalist module was selected to adapt quickly. In contrast, the specialist modules were selected when they more accurately predicted the changing environment than the generalist, as during random schedules; this resulted in consolidated memory specialized to each environment, but only when the ratio of learning rates of the generalist to specialists was relatively small. This dynamic selection process plays a crucial role in explaining the individual differences observed in motor learning abilities.
Permissive and instructiveHoxcodes govern limb positioning
Authors: Wang Yajun , Hintze Maik , Wang Jinbao , Petzsch Patrick , Köhrer Karl , Tao Hengxun , Cheng Longfei , Zhou Peng , Wang Jianlin , Liao Zhaofu , Qi Xufeng , Cai Dongqing , Bartolomaeus Thomas , Schilling Karl , Wilting Joerg , Kuerten Stefanie , Koentges Georgy , Patel Ketan , Pu Qin , Huang Ruijin
Published: July 2024

The positioning of limbs along the anterior-posterior axis varies widely across vertebrates. The mechanisms controlling this feature remain to be fully understood. For over 30 years, it has been speculated thatHoxgenes play a key role in this process but evidence supporting this hypothesis has been largely indirect. In this study, we employed loss- and gain-of-functionHoxgene variants in chick embryos to address this issue. Using this approach, we found thatHox4/5genes are necessary but insufficient for forelimb formation. Within theHox4/5expression domain,Hox6/7genes are sufficient for reprogramming of neck lateral plate mesoderm to form an ectopic limb bud, thereby inducing forelimb formation anterior to the normal limb field. Our findings demonstrate that the forelimb program depends on the combinatorial actions of theseHoxgenes. We propose that during the evolutionary emergence of the neck,Hox4/5provide permissive cues for forelimb formation throughout the neck region, while the final position of the forelimb is determined by the instructive cues ofHox6/7in the lateral plate mesoderm.

Impact statement

Elucidation of theHoxcode defining forelimb positioning provides novel insights in lateral plate mesoderm patterning and the integration of vertebrate column structure and limb positioning.

Classification

Development --- developmental biology
A third kind of episodic memory: Context familiarity is distinct from item familiarity and recollection
Authors: Addante Richard J. , Clise Evan , Waechter Randall , Bengson Jesse , Drane Daniel L. , Perez-Caban Jahdiel
Published: July 2024

Episodic memory is accounted for with two processes: ‘familiarity’ when generally recognizing an item and ‘recollection’ when retrieving the full contextual details bound with the item. Paradoxically, people sometimes report contextual information as familiar but without recollecting details, which is not easily accounted for by existing theories. We tested a combination of item recognition confidence and source memory, focusing upon ‘item-only hits with source unknown’ (‘item familiarity’), ‘low-confidence hits with correct source memory’ (‘context familiarity’), and ‘high-confidence hits with correct source memory’ (‘recollection’). Results across multiple within-subjects (trial-wise) and between subjects (individual variability) levels indicated these were behaviorally and physiologically distinct. Behaviorally, a crossover interaction was evident in response times, with context familiarity being slower than each condition during item recognition, but faster during source memory. Electrophysiologically, a Condition x Time x Location triple dissociation was evident in event-related potentials (ERPs), which was then independently replicated. Context familiarity exhibited an independent negative central effect from 800-1200 ms, differentiated from positive ERPs for item-familiarity (400 to 600 ms) and recollection (600 to 900 ms). These three conditions thus reflect mutually exclusive, fundamentally different processes of episodic memory. Context familiarity is a third distinct process of episodic memory.

Memory for past events is widely believed to operate through two different processes: one called ‘recollection’ when retrieving confident, specific details of a memory, and another called ‘familiarity’ when only having an unsure but conscious awareness that an item was experienced before. When people successfully retrieve details such as the source or context of a prior event, it has been assumed to reflect recollection. We demonstrate that familiarity of context is functionally distinct from familiarity of items and recollection and offer a new, tri-component model of memory. The three memory responses were differentiated across multiple behavioral and brain wave measures. What has traditionally been thought to be two kinds of memory processes are actually three, becoming evident when using sensitive enough multi-measures. Results are independently replicated across studies from different labs. These data reveal that context familiarity is a third process of human episodic memory.

Graphical Abstract
SmartImpute: A Targeted Imputation Framework for Single-cell Transcriptome Data
Authors: Yao Sijie , Yu Xiaoqing , Wang Xuefeng
Published: July 2024

Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity and tissue transcriptomic complexity. However, the high frequency of dropout events in scRNA-seq data complicates downstream analyses such as cell type identification and trajectory inference. Existing imputation methods address the dropout problem but face limitations such as high computational cost and risk of over-imputation. We present SmartImpute, a novel computational framework designed for targeted imputation of scRNA-seq data. SmartImpute focuses on a predefined set of marker genes, enhancing the biological relevance and computational efficiency of the imputation process while minimizing the risk of model misspecification. Utilizing a modified Generative Adversarial Imputation Network architecture, SmartImpute accurately imputes the missing gene expression and distinguishes between true biological zeros and missing values, preventing overfitting and preserving biologically relevant zeros. To ensure reproducibility, we also provide a function based on the GPT4 model to create target gene panels depending on the tissue types and research context. Our results, based on scRNA-seq data from head and neck squamous cell carcinoma and human bone marrow, demonstrate that SmartImpute significantly enhances cell type annotation and clustering accuracy while reducing computational burden. Benchmarking against other imputation methods highlights SmartImpute’s superior performance in terms of both accuracy and efficiency. Overall, SmartImpute provides a lightweight, efficient, and biologically relevant solution for addressing dropout events in scRNA-seq data, facilitating deeper insights into cellular heterogeneity and disease progression. Furthermore, SmartImpute’s targeted approach can be extended to spatial omics data, which also contain many missing values.