bluuebunny/crossref_metadata_2025 huggingface dataset:
The prediction of distant metastasis risk for male breast cancer patients based on an interpretable machine learning model
Authors: Zhao Xuhai , Jiang Cong
Published: April 2023

Objectives

This research was designed to compare the ability of different machine learning (ML) models and nomogram to predict distant metastasis in male breast cancer (MBC) patients and to interpret the optimal ML model by SHapley Additive exPlanations (SHAP) framework.

Methods

Four powerful ML models were developed using data from male breast cancer (MBC) patients in the SEER database between 2010 and 2015 and MBC patients from our hospital between 2010 and 2020. The area under curve (AUC) and Brier score were used to assess the capacity of different models. The Delong test was applied to compare the performance of the models. Univariable and multivariable analysis were conducted using logistic regression.

Results

Of 2351 patients were analyzed; 168 (7.1%) had distant metastasis (M1); 117 (5.0%) had bone metastasis, and 71 (3.0%) had lung metastasis. The median age at diagnosis is 68.0 years old. Most patients did not receive radiotherapy (1723, 73.3%) or chemotherapy (1447, 61.5%). The XGB model was the best ML model for predicting M1 in MBC patients. It showed the largest AUC value in the tenfold cross validation (AUC:0.884; SD:0.02), training (AUC:0.907; 95% CI: 0.899—0.917), testing (AUC:0.827; 95% CI: 0.802—0.857) and external validation (AUC:0.754; 95% CI: 0.739—0.771) sets. It also showed powerful ability in the prediction of bone metastasis (AUC: 0.880, 95% CI: 0.856—0.903 in the training set; AUC: 0.823, 95% CI:0.790—0.848 in the test set; AUC: 0.747, 95% CI: 0.727—0.764 in the external validation set) and lung metastasis (AUC: 0.906, 95% CI: 0.877—0.928 in training set; AUC: 0.859, 95% CI: 0.816—0.891 in the test set; AUC: 0.756, 95% CI: 0.732—0.777 in the external validation set). The AUC value of the XGB model was larger than that of nomogram in the training (0.907 vs 0.802) and external validation (0.754 vs 0.706) sets.

Conclusions

The XGB model is a better predictor of distant metastasis among MBC patients than other ML models and nomogram; furthermore, the XGB model is a powerful model for predicting bone and lung metastasis. Combining with SHAP values, it could help doctors intuitively understand the impact of each variable on outcome.
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants
Authors: Alemany Silvia , Soler-Artigas María , Cabana-Domínguez Judit , Fakhreddine Dana , Llonga Natalia , Vilar-Ribó Laura , Rodríguez-Urrutia Amanda , Palacio Judit , González-Castro Ana María , Lobo Beatriz , Alonso-Cotoner Carmen , Simrén Magnus , Santos Javier , Ramos-Quiroga Josep Antoni , Ribasés Marta
Published: April 2023

Background

Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them.

Methods

We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date.

Results

IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety.

Conclusions

These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.
Vaccination with recombinant Lactococcus lactis expressing HA1-IgY Fc fusion protein provides protective mucosal immunity against H9N2 avian influenza virus in chickens
Authors: Zhang Ruihua , Xu Tong , Li Ziping , Li Longfei , Li Chunhong , Li Xinrui , Wang Zhiyue , Wang Shaohua , Wang Xuejing , Zhang Hongliang
Published: April 2023

Background

H9N2 virus is mainly transmitted through the respiratory mucosal pathway, so mucosal immunity is considered to play a good role in controlling avian influenza infection. It is commonly accepted that no adequate mucosal immunity is achieved by inactivated vaccines, which was widely used to prevent and control avian influenza virus infection. Thus, an improved vaccine to induce both mucosal immunity and systemic immunity is urgently required to control H9N2 avian influenza outbreaks in poultry farms.

Methods

In this study, we constructed a novel Lactococcus lactis (L. lactis) strain expressing a recombinant fusion protein consisting of the HA1 proteins derived from an endemic H9N2 virus strain and chicken IgY Fc fragment. We evaluated the immunogenicity and protective efficacy of this recombinant L. lactis HA1-Fc strain.

Results

Our data demonstrated that chickens immunized with L. lactis HA1-Fc strain showed significantly increased levels of serum antibodies, mucosal secretory IgA, T cell-mediated immune responses, and lymphocyte proliferation. Furthermore, following challenge with H9N2 avian influenza virus, chickens immunized with L. lactis HA1-Fc strain showed reduced the weight loss, relieved clinical symptoms, and decreased the viral titers and the pathological damage in the lung. Moreover, oropharyngeal and cloacal shedding of the H9N2 influenza virus was detected in chicken immunized with L. lactis HA1-Fc after infection, the results showed the titer was low and reduced quickly to reach undetectable levels at 7 days after infection.

Conclusion

Our data showed that the recombinant L. lactis HA1-Fc strain could induce protective mucosal and systemic immunity, and this study provides a theoretical basis for improving immune responses to prevent and control H9N2 virus infection.
The role of doulas in providing breastfeeding support during the COVID-19 pandemic
Authors: Ochapa Monica , Baptiste-Roberts Kesha , Barrett Sharon E. , Animasahun Adeola , Bronner Yvonne
Published: April 2023

Background

Doulas have been instrumental in providing breastfeeding support to nursing mothers before and during the COVID-19 pandemic, as they can significantly impact a mother's ability to initiate and maintain breastfeeding. However, the COVID-19 pandemic, subsequent lockdowns, and social isolation created challenges for nursing mothers to access doulas' services, usually provided in person. In this study, we examined the role of doulas in providing breastfeeding support during the COVID-19 pandemic, exploring adaptation to COVID-19 guidelines and the challenges doulas face in providing breastfeeding support during the pandemic.

Methods

A systematic review was conducted following the PRISMA guidelines. Thirteen scientific databases and twenty peer-reviewed journals were searched for journal articles published in English between January 2020 and March 2022 using key search terms (e.g., Doula, Breastfeeding, COVID-19). Studies evaluating the role of doulas in providing breastfeeding support during COVID-19, and the impact of COVID-19 Guidelines on doula services, were included. Two reviewers independently performed the risk of bias assessment and data extraction. Summative content analysis was used to analyze the data.

Results

The majority of studies were conducted in developed nations. This systematic review includes eight articles, four qualitative, one survey, two mixed-methods studies, and one prospective research study. Seven of the eight studies were conducted in the United States, and the eighth was conducted in multiple countries. These studies have three main themes: (1) virtual breastfeeding support provided by doulas during the pandemic; (2) remote social support provided by doulas to breastfeeding mothers during the pandemic; and (3) barriers to doula service delivery due to COVID-19 restrictions, primarily the exclusion of doulas as essential workers. The eight studies showed that doulas found innovative ways to serve the needs of birthing and nursing mothers during the difficulties brought on by the pandemic.

Conclusion

Doulas provided breastfeeding support during the COVID-19 pandemic by utilizing innovative service delivery methods while navigating changes in COVID-19 guidance. However, system-level integration of doulas' work and the acknowledgment of doulas as essential healthcare providers are needed to enhance doula service delivery capacity, especially during a pandemic, to help improve maternal health outcomes.
Short and mid-term effects of modified release technique in rheumatic mitral valve repair
Authors: Chong Hoshun , Gao Yaxuan , Xue Yunxing , Zhu Xiyu , Li Jie , Wang Junxia , Zhang He , Wang Dongjin , Cao Hailong
Published: April 2023

Objective

Repair or replacement remains debatable in rheumatic heart disease. To regain optimal mean transvalvular pressure gradients and end-diastolic peak flow velocity, the modified release technique combined peeling in the anterior leaflet and separated the shortened chordal. In the end, the short and mid-term outcomes of the modified release technique were evaluated.

Methods

We retrospectively analyzed a series of 128 patients with rheumatic mitral stenosis, from January 2018 to July 2021 in our center. All patients undergoing mitral valve repair were using the modified release technique. The effect of mitral valve repair was evaluated by intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography.

Results

All the 128 patients successfully repaired the mitral valve. The intraoperative transesophageal echocardiography showed trivial or mild regurgitation. The aortic valve was repaired without obvious regurgitation in 12 cases, 5 cases received an aortic valve replacement, 89 cases underwent tricuspid annuloplasty. There were no blood transfusions in most patients, no deaths nor complications during peri-operation, also, no deaths and adverse events were observed during the follow-up period from 3 to 42 months. During the follow-up, 122 cases had no mitral valve regurgitation and 2 cases of moderate regurgitation, 4 cases of mild to moderate regurgitation. The mean peak flow velocity was 1.2 ± 0.3 m / s, no new-onset stenosis occurred.

Conclusion

Modified release technique is safe and feasible. Its durability is acceptable in the short and mid-term, with no new-onset stenosis during the follow-up.
Therapist competencies in the context of group-based exercise programs in medical rehabilitation: a qualitative study with patients and exercise therapists from Germany
Authors: Schuber André Arik , Gernert Madeleine , Schaller Andrea
Published: April 2023

Background

Group-based exercise programs account for nearly half of exercise therapy services provided in German medical rehabilitation facilities. However, information about necessary therapist competencies for the successful execution of these programs is sparse. Thus, the aim of this qualitative study was to explore relevant therapist competencies in the context of group-based exercise programs from the patients’ and therapists’ perspective.

Methods

Semi-structured interviews were conducted with five rehabilitation patients following a 3-week inpatient orthopedic rehabilitation program as well as five exercise therapists with work experience in group-based exercise therapy. Data were analyzed using structuring content analysis according to Kuckartz.

Results

From 155 topic-related text passages, collected over 10 interviews, four competency categories with 16 subcategories and respective characteristics were identified. In addition to professional expertise like biomedical knowledge, exercise therapists were expected to possess a multitude of didactic-methodological, personal, and social-communicative abilities.

Conclusion

Our results suggest that the psychosocial, behavioral and educational goals of group-based exercise programs necessitate a wide range of therapist competencies. These conform to the multidimensional nature of exercise therapy and should therefore be covered in vocational and continuing education.
Stable frequency transfer for clock synchronization for telecom networks
Authors: Wang Xiaocheng , Han Qiaoni , Li Yupeng , Han Liang
Published: April 2023

A stable and reliable clock synchronization system that transfers reference clocks to nodes is essential for telecom networks. Mainly, the clock synchronization of telecom networks is carried out through satellite links. However, for the evolving ubiquitous wireless communications, especially in some harsh environments, such as underground and trenches, the satellite-based clock synchronization scheme bears inevitable obstacles, which may cause strategic risks for the telecom networks, since no control and manipulation can be imposed on the satellite systems. Therefore, to ensure the robust operation of telecom networks with performance guarantees, some auxiliary means are desirable to assist clock synchronization that is solely based on satellite links. In this article, we report a phase-stabilized frequency signal transmission on branching optical fiber for clock synchronization for telecom networks. Particularly, the phase fluctuation due to optical carriers separation link and fiber link is compensated by a feedback network, which employs a high-precision voltage-controlled oscillator in the phase-locked loop to drive the acousto-optic frequency shifter for fast phase correction. Furtherly, the factors that cause performance limitations of the frequency distribution system are analyzed. Eventually, the experiment results obtained show that a stabilized fiber-optic frequency transfer scheme can be used as a reliable method for clock synchronization with high accuracy.
The X-factor in ART: does the use of assisted reproductive technologies influence DNA methylation on the X chromosome?
Authors: Romanowska Julia , Nustad Haakon E. , Page Christian M. , Denault William R. P. , Lee Yunsung , Magnus Maria C. , Haftorn Kristine L. , Gjerdevik Miriam , Novakovic Boris , Saffery Richard , Gjessing Håkon K. , Lyle Robert , Magnus Per , Håberg Siri E. , Jugessur Astanand
Published: April 2023

Background

Assisted reproductive technologies (ART) may perturb DNA methylation (DNAm) in early embryonic development. Although a handful of epigenome-wide association studies of ART have been published, none have investigated CpGs on the X chromosome. To bridge this knowledge gap, we leveraged one of the largest collections of mother–father–newborn trios of ART and non-ART (natural) conceptions to date to investigate sex-specific DNAm differences on the X chromosome. The discovery cohort consisted of 982 ART and 963 non-ART trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa). To verify our results from the MoBa cohort, we used an external cohort of 149 ART and 58 non-ART neonates from the Australian ‘Clinical review of the Health of adults conceived following Assisted Reproductive Technologies’ (CHART) study. The Illumina EPIC array was used to measure DNAm in both datasets. In the MoBa cohort, we performed a set of X-chromosome-wide association studies (‘XWASs’ hereafter) to search for sex-specific DNAm differences between ART and non-ART newborns. We tested several models to investigate the influence of various confounders, including parental DNAm. We also searched for differentially methylated regions (DMRs) and regions of co-methylation flanking the most significant CpGs. Additionally, we ran an analogous model to our main model on the external CHART dataset.

Results

In the MoBa cohort, we found more differentially methylated CpGs and DMRs in girls than boys. Most of the associations persisted after controlling for parental DNAm and other confounders. Many of the significant CpGs and DMRs were in gene-promoter regions, and several of the genes linked to these CpGs are expressed in tissues relevant for both ART and sex (testis, placenta, and fallopian tube). We found no support for parental DNAm-dependent features as an explanation for the observed associations in the newborns. The most significant CpG in the boys-only analysis was in UBE2DNL, which is expressed in testes but with unknown function. The most significant CpGs in the girls-only analysis were in EIF2S3 and AMOT. These three loci also displayed differential DNAm in the CHART cohort.

Conclusions

Genes that co-localized with the significant CpGs and DMRs associated with ART are implicated in several key biological processes (e.g., neurodevelopment) and disorders (e.g., intellectual disability and autism). These connections are particularly compelling in light of previous findings indicating that neurodevelopmental outcomes differ in ART-conceived children compared to those naturally conceived.
Cardiotoxicity of chloroquine and hydroxychloroquine through mitochondrial pathway
Authors: Seydi Enayatollah , Hassani Mozhgan Karbalaei , Naderpour Saghi , Arjmand Abdollah , Pourahmad Jalal
Published: April 2023

Background

Medical therapies can cause cardiotoxicity. Chloroquine (QC) and hydroxychloroquine (HQC) are drugs used in the treatment of malaria and skin and rheumatic disorders. These drugs were considered to help treatment of coronavirus disease (COVID-19) in 2019. Despite the low cost and availability of QC and HQC, reports indicate that this class of drugs can cause cardiotoxicity. The mechanism of this event is not well known, but evidence shows that QC and HQC can cause cardiotoxicity by affecting mitochondria and lysosomes.

Methods

Therefore, our study was designed to investigate the effects of QC and HQC on heart mitochondria. In order to achieve this aim, mitochondrial function, reactive oxygen species (ROS) level, mitochondrial membrane disruption, and cytochrome c release in heart mitochondria were evaluated. Statistical significance was determined using the one-way and two-way analysis of variance (ANOVA) followed by post hoc Tukey to evaluate mitochondrial succinate dehydrogenase (SDH) activity and cytochrome c release, and Bonferroni test to evaluate the ROS level, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling.

Results

Based on ANOVA analysis (one-way), the results of mitochondrial SDH activity showed that the IC50 concentration for CQ is 20 µM and for HCQ is 50 µM. Based on two-way ANOVA analysis, the highest effect of CQ and HCQ on the generation of ROS, collapse in the MMP, and mitochondrial swelling were observed at 40 µM and 100 µM concentrations, respectively (p < 0.05). Also, the highest effect of these two drugs has been observed in 60 min (p < 0.05). The statistical results showed that compared to CQ, HCQ is able to cause the release of cytochrome c from mitochondria in all applied concentrations (p < 0.05).

Conclusions

The results suggest that QC and HQC can cause cardiotoxicity which can lead to heart disorders through oxidative stress and disfunction of heart mitochondria.
Metapangenomics of wild and cultivated banana microbiome reveals a plethora of host-associated protective functions
Authors: Singh Simrandeep , Aghdam Shiva A. , Lahowetz Rachel M. , Brown Amanda M. V.
Published: April 2023

Background

Microbiomes are critical to plants, promoting growth, elevating stress tolerance, and expanding the plant’s metabolic repertoire with novel defense pathways. However, generally microbiomes within plant tissues, which intimately interact with their hosts, remain poorly characterized. These endospheres have become a focus in banana (Musa spp.)—an important plant for study of microbiome-based disease protection. Banana is important to global food security, while also being critically threatened by pandemic diseases. Domestication and clonal propagation are thought to have depleted protective microbiomes, whereas wild relatives may hold promise for new microbiome-based biological controls. The goal was to compare metapangenomes enriched from 7 Musa genotypes, including wild and cultivated varieties grown in sympatry, to assess the host associations with root and leaf endosphere functional profiles.

Results

Density gradients successfully generated culture-free microbial enrichment, dominated by bacteria, with all together 24,325 species or strains distinguished, and 1.7 million metagenomic scaffolds harboring 559,108 predicted gene clusters. About 20% of sequence reads did not match any taxon databases and ~ 62% of gene clusters could not be annotated to function. Most taxa and gene clusters were unshared between Musa genotypes. Root and corm tissues had significantly richer endosphere communities that were significantly different from leaf communities. Agrobacterium and Rhizobium were the most abundant in all samples while Chitinophagia and Actinomycetia were more abundant in roots and Flavobacteria in leaves. At the bacterial strain level, there were > 2000 taxa unique to each of M. acuminata (AAA genotype) and M. balbisiana (B-genotype), with the latter ‘wild’ relatives having richer taxa and functions. Gene ontology functional enrichment showed core beneficial functions aligned with those of other plants but also many specialized prospective beneficial functions not reported previously. Some gene clusters with plant-protective functions showed signatures of phylosymbiosis, suggesting long-standing associations or heritable microbiomes in Musa.

Conclusions

Metapangenomics revealed key taxa and protective functions that appeared to be driven by genotype, perhaps contributing to host resistance differences. The recovery of rich novel taxa and gene clusters provides a baseline dataset for future experiments in planta or in vivo bacterization or engineering of wild host endophytes.
Food Provision at the Olympic Games in the New Millennium: A Meta-narrative Review
Authors: Pelly Fiona E. , Tweedie Judith , O’Connor Helen
Published: April 2023

Background and objective

The objective of this meta-narrative review was to identify, organise and map the literature on food provision and nutrition support at the summer and winter Olympic and Paralympic Games (OPG)  and similar major competition events over the past 21 years. This builds on a comprehensive update of a previous historical review of the evolution of food provision at the summer Olympic Games up until 2000 and considers contemporary issues such as the global pandemic and sustainability goals.

Methods

A range of sources included primary research and review articles, edited book chapters, theses, conference papers or abstracts, International Olympic Committee reports, Organising Committees’ food vision and post-Games reports, independent professional reports, and media and periodicals including magazines and trade journals. The search strategy included four steps: a database search that complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews criteria, a search of the Olympic Studies Centre, a review of reference lists for unpublished sources, and a Google search for additional media reports. The researchers followed an iterative process where emerging narratives were discussed, recorded and refined as data were extracted.

Results

The data from 229 records were extracted into a spreadsheet and grouped according to the type of evidence and specific event, then presented chronologically to give a perspective on the development of food provision and nutrition support. Eleven narratives emerged from the data extraction: ‘description of meals, menus and food’, ‘vision of the food provision’, ‘food safety’, ‘catering company involvement’, ‘sponsorship or contracts with food companies’, ‘athlete perspective’, ‘stakeholder perspective’, ‘athlete food intake,’ ‘nutrition input in food provision’, ‘food environment’ and ‘sustainability’.

Conclusion

Results suggest that athletes' dining expectations, organising committee budgets, expert input and current global trends have led to food delivery changes. The OPG food environment has the capacity to positively influence the dietary choices of athletes and teams, while evolving to meet contemporary global challenges such as COVID-19 and sustainability targets.
Survival of oral tongue cancer in low middle-income country: a cohort study
Authors: Ukrani Ronika Devi , Danish Muhammad Hassan , Ikram Mubasher , Nathani Karim Rizwan , Salim Shaharyar , Muhammad Adnan Yar , Rozi Shafquat , Zahid Nida , Iftikhar Haissan
Published: April 2023

Introduction

The incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing. OTSCC is comparatively higher in our region owing to the consumption of tobacco, beetle nut, alcohol, and poor oral hygiene. There is paucity of survival data for OTSCC from our high-burden region.

Background

There is paucity of survival data for OTSCC from our high-burden region, we aimed to determine 5-year overall and disease-free survival of patients with OTSCC.

Methods

A retrospective chart review was conducted for all the patients treated for oral tongue squamous cell carcinoma from January 2000 and December 2013. The data on overall survival and disease-free survival was collected via telephonic interviews up till 2018. Kaplan Meier curves were plotted to graphically represent survival.

Results

A total of 131 patients were included. The mean age of the patients was 49.4 ± 12.98 years, with most patients being male (65.9%). The most common tumor stage was T2 (55.1%) and the most common nodal stage was N0 (57.7%). Five-year disease-free survival was 59.2%, and overall survival was 60.7%. Overall survival dropped steeply from 84.4 to 7.5% in patients who developed recurrence in our cohort.

Conclusion

The most significant factor influencing the survival of patients with OTSCC is tumor recurrence. 5-year recurrence-free survival was 84.4% which is greater than reported in literature. This could be due to the low incidence of perineural and perivascular invasion in our population. Further research on factors leading to recurrence should be done.
Prevalence and clinico-bacteriological aspects of chronic suppurative otitis media at the Renaissance University Hospital in N'Djamena, Chad
Authors: Taoussi Aboubakar Assidick , Malloum Mahamat Seïd Mahamat , Ali Yusra Aboulbachar
Published: April 2023

Background

Chronic suppurative otitis media is a major cause of hearing impairment and morbidity in poor socioeconomic developing countries.

Objectives

To determine the prevalence of chronic suppurative otitis media in a tertiary care hospital and to analyze its clinico-bacteriological aspects.

Methods

This is a cross-sectional, descriptive and analytical study conducted at the ENT and Head and Neck Surgery Department in the Renaissance University Hospital in N'Djamena, Chad. All the patients that were diagnosed with chronic suppurative otitis media from 1 January 2017 to 31 December 2019 were included.

Results

The hospital prevalence was 6.1%. The sex ratio (male/female) was 1.09. The median age of patients was 28 years with [1 to 74 years]. The median time from the onset of otorrhea to coming for medical consultation was 6 years with [4 months to 42 years]. The main symptom associated with otorrhea was hearing impairment which was in 55.6% of cases (n = 50). Perforations ≥ ¾ of the tympanic membrane surface were noted in 51.3% of cases (n = 60). The tympanic cavity floor was erythematous in 49.6% of cases (n = 58) and erythematous with a discharge in 42.7% of cases (n = 50). There was an association between the size of the perforation and the appearance of the tympanic mucosa (p = 0.003), and between the age of the disease and the side of the ear affected with chronic suppurative otitis media (p = 0.016). The culture positivity rate was 86.1% (n = 31) and with two other microbial cases. Staphylococcus aureus was isolated in 28.1% of cases (n = 9) followed by Pseudomonas aeruginosa which was 25% of the cases (n = 8).

Conclusion

Chronic suppurative otitis media affects both children and adults. Delay in medical consultation to the ENT department is relatively high. Staphylococcus aureus and Pseudomonas aeruginosa are the most common causes.
Harmonizing Biopredictive Methodologies Through the Product Quality Research Institute (PQRI) Part I: Biopredictive Dissolution of Ibuprofen and Dipyridamole Tablets
Authors: Tsume Yasuhiro , Ashworth Lee , Bermejo Marival , Cheng Joan , Cicale Vincent , Dressman Jennifer , Fushimi Masahiro , Gonzalez-Alvarez Isabel , Guo Yiwang , Jankovsky Corinne , Lu Xujin , Matsui Kazuki , Patel Sanjaykumar , Sanderson Natalie , Sun Changquan Calvin , Thakral Naveen K. , Yamane Miki , Zöller Laurin
Published: April 2023

Assessing in vivo performance to inform formulation selection and development decisions is an important aspect of drug development. Biopredictive dissolution methodologies for oral dosage forms have been developed to understand in vivo performance, assist in formulation development/optimization, and forecast the outcome of bioequivalence studies by combining them with simulation tools to predict plasma profiles in humans. However, unlike compendial dissolution methodologies, the various biopredictive methodologies have not yet been harmonized or standardized. This manuscript presents the initial phases of an effort to develop best practices and move toward standardization of the biopredictive methodologies through the Product Quality Research Institute (PQRI, https://pqri.org) entitled “The standardization of in vitro predictive dissolution methodologies and in silico bioequivalence study Working Group.” This Working Group (WG) is comprised of participants from 10 pharmaceutical companies and academic institutes. The project will be accomplished in a total of five phases including assessing the performance of dissolution protocols designed by the individual WG members, and then building “best practice” protocols based on the initial dissolution profiles. After refining the “best practice” protocols to produce equivalent dissolution profiles, those will be combined with physiologically based biopharmaceutics models (PBBM) to predict plasma profiles. In this manuscript, the first two of the five phases are reported, namely generating biopredictive dissolution profiles for ibuprofen and dipyridamole and using those dissolution profiles with PBBM to match the clinical plasma profiles. Key experimental parameters are identified, and this knowledge will be applied to build the “best practice” protocol in the next phase.

Graphical Abstract
Burosumab vs Phosphate/Active Vitamin D in Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis by Dose Level
Authors: Imel Erik A , Glorieux Francis H , Whyte Michael P , Portale Anthony A , Munns Craig F , Nilsson Ola , Simmons Jill H , Padidela Raja , Namba Noriyuki , Cheong Hae Il , Pitukcheewanont Pisit , Sochett Etienne , Högler Wolfgang , Muroya Koji , Tanaka Hiroyuki , Gottesman Gary S , Biggin Andrew , Perwad Farzana , Chen Angel , Roberts Mary Scott , Ward Leanne M
Published: April 2023

Context

In an open-label, randomized, controlled, phase 3 trial in 61 children aged 1 to 12 years with X-linked hypophosphatemia (XLH), burosumab improved rickets vs continuing conventional therapy with active vitamin D and phosphate.

Objective

We conducted an analysis to determine whether skeletal responses differed when switching to burosumab vs continuing higher or lower doses of conventional therapy.

Methods

Conventional therapy dose groups were defined as higher-dose phosphate [greater than 40 mg/kg] (HPi), lower-dose phosphate [40 mg/kg or less] (LPi), higher-dose alfacalcidol [greater than 60 ng/kg] or calcitriol [greater than 30 ng/kg] (HD), and lower-dose alfacalcidol [60 ng/kg or less] or calcitriol [30 ng/kg or less] (LD).

Results

At week 64, the Radiographic Global Impression of Change (RGI-C) for rickets was higher (better) in children randomly assigned to burosumab vs conventional therapy for all prebaseline dose groups: HPi (+1.72 vs +0.67), LPi (+2.14 vs +1.08), HD (+1.90 vs +0.94), LD (+2.11 vs +1.06). At week 64, the RGI-C for rickets was also higher in children randomly assigned to burosumab (+2.06) vs conventional therapy for all on-study dose groups: HPi (+1.03), LPi (+1.05), HD (+1.45), LD (+0.72). Serum alkaline phosphatase (ALP) also decreased in the burosumab-treated patients more than in the conventional therapy group, regardless of on-study phosphate and active vitamin D doses.

Conclusion

Prior phosphate or active vitamin D doses did not influence treatment response after switching to burosumab among children with XLH and active radiographic rickets. Switching from conventional therapy to burosumab improved rickets and serum ALP more than continuing either higher or lower doses of phosphate or active vitamin D.
Successful Treatment of Hypoglycemia With Alpelisib in Pediatric Patients With PIK3CA-Related Overgrowth Spectrum
Authors: Nasomyont Nat , Rutter Meilan M , Backeljauw Philippe F
Published: April 2023

Activating mutations in the PIK3CA gene, causing phosphoinositide 3-kinase (PI3K) hyperactivation, are rare causes of hypoglycemia. We report the novel use of alpelisib (a PI3K inhibitor) for the treatment of hypoketotic, hypoinsulinemic hypoglycemia in 2 children with PIK3CA-related overgrowth spectrum (PROS). Patient 1 was a 7-month-old girl who presented with a hypoglycemic seizure. Despite nutritional management including continuous feeds, she continued to have frequent hypoglycemia. At age 2.8 years, alpelisib was started at 50 mg daily and titrated to 100 mg daily. She was weaned off nocturnal continuous feeds by 8 months. She developed colitis when the alpelisib dose was increased to 125 mg, but this resolved with a dose decrease and medical management. At age 5.3 years, she was doing well with rare hypoglycemia. Her accelerated growth stabilized. Patient 2 was a 3-year-old boy who developed hypoglycemia in early infancy. Alpelisib 50 mg daily was started due to recurrent hypoglycemia despite nutritional management. He came off continuous feeds after 4 months, with decreased hypoglycemia frequency. At age 4.5 years, he had not experienced side effects from treatment. In conclusion, alpelisib appears to be effective in decreasing PROS-related hypoglycemia frequency and severity and should be considered for refractory hypoglycemia in this condition.
Coethnic, Multicultural, or Cosmopolitan? Cultural Citizenship, Enfranchisement, and the Contested Category of Korean-Chinese in Globalizing South Korea
Authors: Han Seung-Mi
Published: April 2023

This article deals with the Korean-Chinese politics of recognition in contemporary South Korea. Unlike North Korean settlers who are “technically” embraced from the outset as coethnics, the Korean-Chinese are located in the interstices of the Act on the Employment of Foreign Workers, the Overseas Koreans Act, and the Multicultural Families Support Act. By analyzing how the Korean-Chinese politics of belonging is mediated by competing models of nationalism, multiculturalism, and political participation that Korean-Chinese bring with them from the People’s Republic of China and encounter anew in South Korea, the article puts into relief the various choices available to these migrants and their emotionally-charged disagreements over how to define themselves culturally and politically. Juxtaposing Korean-style multicultural policy with a curiously muted cultural distinctiveness in the Korean-Chinese politics of recognition, the article argues for the importance of cherishing cultural diversity in the public sphere, even for the coethnic politics of belonging.
Training the Ear and Remixing the Archive in Looking for Langston
Authors: Kraeher Rudi
Published: April 2023

This essay argues for a close attention to the use of sound in the audiovisual aesthetics of Isaac Julien's seminal New Queer Cinema film Looking for Langston (1989). The analysis relies on Amber Musser's work on “sensation” as an analytic for corporeal knowledge production and performs a series of close readings that highlight the influential role of musical remixing practices in the film's synchronization of sound and image. Remixing practices such as sampling provide a music-based conceptual vocabulary, which helps to illuminate how the montage of Looking for Langston is structured by its sonic elements. The essay shows how Looking for Langston promotes an open-ended orientation toward the archive that eschews artifact discovery and epistemologies of certainty. Instead, embracing the possibilities of archival work that is guided by our bodily sensations and desires, the film offers an alternative disposition toward queer of color archives that celebrates the possibilities of speculative fantasy, opacity, and disorientation. Furthermore, the essay shows, not only is the film's use of sound interesting in its divergence from the conventions of sound synchronization within many documentary and narrative cinematic forms, but the film is also particularly notable for how it actively draws on practices from contemporary musical culture (specifically late 1980s house music) in order to produce a thoroughly sound-based cinematic montage.
Single-Posterior Revision Surgery for Recurrent Thoracic/Thoracolumbar Spinal Tuberculosis With Kyphosis
Authors: Yang Kai , Feng Chaoshuai , Zheng Bolong , Hui Hua , Kong Lingbo , Yan Liang , Hao Dingjun , He Baorong
Published: April 2023

BACKGROUND AND OBJECTIVES:

The treatment of thoracic/thoracolumbar spinal tuberculosis (STB) remains challenging. The spinal deformity, long disease history, heterogeneous lesion, and poor drug response make the treatment of recurrent and kyphosis cases even more difficult. This study aims to investigate the efficacy and safety of single-posterior revision surgery in patients with recurrent thoracic/thoracolumbar STB and kyphosis.

METHODS:

Patients with recurrent thoracic/thoracolumbar STB with kyphosis and treated with single-posterior debridement, osteotomy, correction, bone graft, and fusion in our center from 2009 to 2019 were enrolled. The clinical data, radiographs, and erythrocyte sedimentation rate (ESR) at different stages were collected. ESR, kyphotic angle, Visual Analog Scale, and neurological functions were analyzed.

RESULTS:

A total of 27 patients (16 male, 11 female) with an average age of 48.4 ± 13.0 years were included. The average surgery time was 320.6 ± 46.4 minutes, and the average estimated blood loss was 1470.6 ± 367.4 mL. From admittance to the latest follow-up, the average Visual Analog Scale significantly reduced from 5.6 ± 1.3 to 0.5 ± 0.7, the average ESR was improved from 69.4 ± 15.8 mm/h to normal, and the average kyphotic angle was corrected from 66.6° ± 11.7° to 34.5° ± 6.6°. For patients with preoperative neurological deficits, their neurological functions were improved to normal. In drug susceptibility tests, 70.5% (11/17) of specimens had bacteria resistant to at least 1 first-line drug.

CONCLUSION:

Single-posterior debridement, osteotomy, correction, bone graft, and fusion are effective and safe in the treatment of recurrent thoracic/thoracolumbar spinal tuberculosis with kyphosis. The drug treatment of recurrent spinal tuberculosis should be carefully tailored.
Three-Dimensional Modeling and Extended Reality Simulations of the Cross-Sectional Anatomy of the Cerebrum, Cerebellum, and Brainstem
Authors: Gurses Muhammet Enes , Hanalioglu Sahin , Mignucci-Jiménez Giancarlo , Gökalp Elif , Gonzalez-Romo Nicolas I. , Gungor Abuzer , Cohen-Gadol Aaron A. , Türe Uğur , Lawton Michael T. , Preul Mark C.
Published: April 2023

BACKGROUND:

Understanding the anatomy of the human cerebrum, cerebellum, and brainstem and their 3-dimensional (3D) relationships is critical for neurosurgery. Although 3D photogrammetric models of cadaver brains and 2-dimensional images of postmortem brain slices are available, neurosurgeons lack free access to 3D models of cross-sectional anatomy of the cerebrum, cerebellum, and brainstem that can be simulated in both augmented reality (AR) and virtual reality (VR).

OBJECTIVE:

To create 3D models and AR/VR simulations from 2-dimensional images of cross-sectionally dissected cadaveric specimens of the cerebrum, cerebellum, and brainstem.

METHODS:

The Klingler method was used to prepare 3 cadaveric specimens for dissection in the axial, sagittal, and coronal planes. A series of 3D models and AR/VR simulations were then created using 360° photogrammetry.

RESULTS:

High-resolution 3D models of cross-sectional anatomy of the cerebrum, cerebellum, and brainstem were obtained and used in creating AR/VR simulations. Eleven axial, 9 sagittal, and 7 coronal 3D models were created. The sections were planned to show important deep anatomic structures. These models can be freely rotated, projected onto any surface, viewed from all angles, and examined at various magnifications.

CONCLUSION:

To our knowledge, this detailed study is the first to combine up-to-date technologies (photogrammetry, AR, and VR) for high-resolution 3D visualization of the cross-sectional anatomy of the entire human cerebrum, cerebellum, and brainstem. The resulting 3D images are freely available for use by medical professionals and students for better comprehension of the 3D relationship of the deep and superficial brain anatomy.
Correlation Among Syrinx Resolution, Cervical Sagittal Realignment, and Surgical Outcome After Posterior Reduction for Basilar Invagination, Atlantoaxial Dislocation, and Syringomyelia
Authors: Lu Chunli , Duan Wanru , Zhang Can , Du Yueqi , Wang Xinyu , Ma Longbing , Wang Kai , Wu Hao , Chen Zan , Jian Fengzeng
Published: April 2023

BACKGROUND:

The correlation among syrinx resolution, occipitoaxial sagittal alignment, and surgical outcome in long-term follow-up seems to have not been clarified.

OBJECTIVE:

To further explore the relationship between the syrinx resolution and occipitoaxial realignment after posterior reduction and fixation in basilar invagination (BI)-atlantoaxial dislocation (AAD) patients with syringomyelia.

METHODS:

A continuous series of 32 patients with BI-AAD and syringomyelia who received direct posterior reduction met the inclusion criteria of this study. Their clinical and imaging data were analyzed retrospectively. Before surgery and at the last follow-up, we used the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI) to assess the neurological status, respectively. The Pearson correlation coefficient and multiple stepwise regression analysis were used to explore the relevant factors that may affect surgical outcomes.

RESULTS:

There were significant differences in atlantodental interval, clivus-axial angle, occiput-C2 angle (Oc-C2A), cervicomedullary angle (CMA), subarachnoid space (SAS) at the foramen magnum (FM), syrinx size, NDI, and JOA score after surgery compared with those before surgery. ΔCMA and the resolution rate of syrinx/cord as relevant factors were correlated with the recovery rate of JOA (R2 = 0.578, P < .001) and NDI (R2 = 0.369, P < .01). What's more, ΔSAS/FMD (SAS/FM diameter) and ΔOc-C2A were positively correlated with the resolution rate of syrinx/cord (R2 = 0.643, P < .001).

CONCLUSION:

With medulla decompression and occipital-cervical sagittal realignment after posterior reduction and fusion for BI-AAD patients with syringomyelia, the structural remodeling of the craniovertebral junction and occipitoaxial realignment could contribute to syringomyelia resolution.
One-Insertion Stereotactic Brain Biopsy Using In Vivo Optical Guidance—A Case Study
Authors: Wårdell Karin , Klint Elisabeth , Milos Peter , Richter Johan
Published: April 2023

BACKGROUND:

Stereotactic neurosurgical brain biopsies are afflicted with risks of inconclusive results and hemorrhage. Such complications can necessitate repeated trajectories and prolong surgical time.

OBJECTIVE:

To develop and introduce a 1-insertion stereotactic biopsy kit with direct intraoperative optical feedback and to evaluate its applicability in 3 clinical cases.

METHODS:

An in-house forward-looking probe with optical fibers was designed to fit the outer cannula of a side-cutting biopsy kit. A small aperture was made at the tip of the outer cannula and the edges aligned with the optical probe inside. Stereotactic biopsies were performed using the Leksell Stereotactic System. Optical signals were measured in millimeter steps along the preplanned trajectory during the insertion. At the region with the highest 5-aminolevulinic acid (5-ALA)–induced fluorescence, the probe was replaced by the inner cannula, and tissue samples were taken. The waiting time for pathology diagnosis was noted.

RESULTS:

Measurements took 5 to 10 minutes, and the surgeon received direct visual feedback of intraoperative 5-ALA fluorescence, microcirculation, and tissue gray-whiteness. The 5-ALA fluorescence corroborated with the pathological findings which had waiting times of 45, 50, and 75 minutes. Because only 1 trajectory was required and the patient could be prepared for the end of surgery immediately after sampling, this shortened the total surgical time.

CONCLUSION:

A 1-insertion stereotactic biopsy procedure with real-time optical guidance has been presented and successfully evaluated in 3 clinical cases. The method can be modified for frameless navigation and thus has great potential to improve safety and diagnostic yield for both frameless and frame-based neurosurgical biopsy procedures.
The DOT1L-MLLT10 complex regulates male fertility and promotes histone removal during spermiogenesis
Authors: Lin Huijuan , Cossu Isabella G. , Leu N. Adrian , Deshpande Aniruddha J. , Bernt Kathrin M. , Luo Mengcheng , Wang P. Jeremy
Published: April 2023

Histone modifications regulate chromatin remodeling and gene expression in development and diseases. DOT1L, the sole histone H3K79 methyltransferase, is essential for embryonic development. Here, we report that DOT1L regulates male fertility in mouse. DOT1L associates with MLLT10 in testis. DOT1L and MLLT10 localize to the sex chromatin in meiotic and post-meiotic germ cells in an inter-dependent manner. Loss of either DOT1L or MLLT10 leads to reduced testis weight, decreased sperm count and male subfertility. H3K79me2 is abundant in elongating spermatids, which undergo the dramatic histone-to-protamine transition. Both DOT1L and MLLT10 are essential for H3K79me2 modification in germ cells. Strikingly, histones are substantially retained in epididymal sperm from either DOT1L- or MLLT10-deficient mice. These results demonstrate that H3K79 methylation promotes histone replacement during spermiogenesis.
Βιωματικό Εργαστήριο «Σχολικός Εκφοβισμός, Ανθεκτικότητα και Ενσυναίσθηση»
Authors: Γκάτσα Τατιανή
Published: April 2023

Βιωματικό Εργαστήριο «Σχολικός Εκφοβισμός, Ανθεκτικότητα και Ενσυναίσθηση»