bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression variability across cells and species shapes the relationship between renal resident macrophages and infiltrated macrophages
Authors: Ji Xiangjun , Cai Junwei , Liang Lixin , Shi Tieliu , Liu Jinghua
Published: March 2023

Background

Two main subclasses of macrophages are found in almost all solid tissues: embryo-derived resident tissue macrophages and bone marrow-derived infiltrated macrophages. These macrophage subtypes show transcriptional and functional divergence, and the programs that have shaped the evolution of renal macrophages and related signaling pathways remain poorly understood. To clarify these processes, we performed data analysis based on single-cell transcriptional profiling of renal tissue-resident and infiltrated macrophages in human, mouse and rat.

Results

In this study, we (i) characterized the transcriptional divergence among species and (ii) illustrated variability in expression among cells of each subtype and (iii) compared the gene regulation network and (iv) ligand-receptor pairs in human and mouse. Using single-cell transcriptomics, we mapped the promoter architecture during homeostasis.

Conclusions

Transcriptionally divergent genes, such as the differentially TF-encoding genes expressed in resident and infiltrated macrophages across the three species, vary among cells and include distinct promoter structures. The gene regulatory network in infiltrated macrophages shows comparatively better species-wide consistency than resident macrophages. The conserved transcriptional gene regulatory network in infiltrated macrophages among species is uniquely enriched in pathways related to kinases, and TFs associated with largely conserved regulons among species are uniquely enriched in kinase-related pathways.
Identification of alternative splicing events related to fatty liver formation in duck using full-length transcripts
Authors: Wang Yiming , Song Linfei , Ning Mengfei , Hu Jiaxiang , Cai Han , Song Weitao , Gong Daoqing , Liu Long , Smith Jacqueline , Li Huifang , Huang Yinhua
Published: March 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is one of most common diseases in the world. Recently, alternative splicing (AS) has been reported to play a key role in NAFLD processes in mammals. Ducks can quickly form fatty liver similar to human NAFLD after overfeeding and restore to normal liver in a short time, suggesting that ducks are an excellent model to unravel molecular mechanisms of lipid metabolism for NAFLD. However, how alternative splicing events (ASEs) affect the fatty liver process in ducks is still unclear.

Results

Here we identify 126,277 unique transcripts in liver tissue from an overfed duck (77,237 total transcripts) and its sibling control (69,618 total transcripts). We combined these full-length transcripts with Illumina RNA-seq data from five pairs of overfed ducks and control individuals. Full-length transcript sequencing provided us with structural information of transcripts and Illumina RNA-seq data reveals the expressional profile of each transcript. We found, among these unique transcripts, 30,618 were lncRNAs and 1,744 transcripts including 155 lncRNAs and 1,589 coding transcripts showed significantly differential expression in liver tissues between overfed ducks and control individuals. We also detected 27,317 ASEs and 142 of them showed significant relative abundance changes in ducks under different feeding conditions. Full-length transcript profiles together with Illumina RNA-seq data demonstrated that 10 genes involving in lipid metabolism had ASEs with significantly differential abundance in normally fed (control) and overfed ducks. Among these genes, protein products of five genes (CYP4F22, BTN, GSTA2, ADH5, and DHRS2 genes) were changed by ASEs.

Conclusions

This study presents an example of how to identify ASEs related to important biological processes, such as fatty liver formation, using full-length transcripts alongside Illumina RNA-seq data. Based on these data, we screened out ASEs of lipid-metabolism related genes which might respond to overfeeding. Our future ability to explore the function of genes showing AS differences between overfed ducks and their sibling controls, using genetic manipulations and co-evolutionary studies, will certainly extend our knowledge of genes related to the non-pathogenic fatty liver process.
Exploring data reduction strategies in the analysis of continuous pressure imaging technology
Authors: Peng Mingkai , Southern Danielle A. , Ocampo Wrechelle , Kaufman Jaime , Hogan David B. , Conly John , Baylis Barry W. , Stelfox Henry T. , Ho Chester , Ghali William A.
Published: March 2023

Background

Science is becoming increasingly data intensive as digital innovations bring new capacity for continuous data generation and storage. This progress also brings challenges, as many scientific initiatives are challenged by the shear volumes of data produced. Here we present a case study of a data intensive randomized clinical trial assessing the utility of continuous pressure imaging (CPI) for reducing pressure injuries.

Objective

To explore an approach to reducing the amount of CPI data required for analyses to a manageable size without loss of critical information using a nested subset of pressure data.

Methods

Data from four enrolled study participants excluded from the analytical phase of the study were used to develop an approach to data reduction. A two-step data strategy was used. First, raw data were sampled at different frequencies (5, 30, 60, 120, and 240 s) to identify optimal measurement frequency. Second, similarity between adjacent frames was evaluated using correlation coefficients to identify position changes of enrolled study participants. Data strategy performance was evaluated through visual inspection using heat maps and time series plots.

Results

A sampling frequency of every 60 s provided reasonable representation of changes in interface pressure over time. This approach translated to using only 1.7% of the collected data in analyses. In the second step it was found that 160 frames within 24 h represented the pressure states of study participants. In total, only 480 frames from the 72 h of collected data would be needed for analyses without loss of information. Only ~ 0.2% of the raw data collected would be required for assessment of the primary trial outcome.

Conclusions

Data reduction is an important component of big data analytics. Our two-step strategy markedly reduced the amount of data required for analyses without loss of information. This data reduction strategy, if validated, could be used in other CPI and other settings where large amounts of both temporal and spatial data must be analysed.
Idiopathic non-cirrhotic portal hypertension in a patient with Talaromyces marneffei infection: a case report
Authors: Ye Xiuling , Quan Xin , Guo Xu , Wang Zhidong , Wu Hao
Published: March 2023

Background

The etiopathogenesis of idiopathic non-cirrhotic portal hypertension (INCPH) is so far poorly understood. Altered immunity, blood diseases, infections, congenital defects and drug exposure have been documented in a part of patients with INCPH owing to increased recognition of the disorder in patients with HIV, or various haematological disorders or autoimmune diseases. We aim to discuss the possible etiopathogenesis of INCPH.

Case presentation

We reported that a patient with intestinal infection of T. Marneffei and hyper-IgE syndrome, a group of rare primary immunodeficiency disorders, was finally diagnosed with INCPH for gastroesophageal variceal bleeding. The diagnosis was mainly based on histopathological features. Transjugular intrahepatic portosystemic shunt was performed and there was no recurrence of melena during the six-month follow-up.

Conclusion

In the context of immunodeficiency, INCPH may associated with intestinal infections. Thus, screening for enterogenic infection and immunological disorders in patients with unexplained portal hypertension is necessary.
Association of scrub typhus with incidence of dementia: a nationwide population-based cohort study in Korea
Authors: Kim Jooyun , Seok Hyeri , Jeon Ji Hoon , Choi Won Suk , Seo Gi Hyeon , Park Dae Won
Published: March 2023

Background

Scrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data.

Method

This population-based cohort study enrolled patients aged 60–89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer’s disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity.

Results

During the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10–1.15, p < 0.001). The Kaplan–Meier curves for time to cumulative incidence of dementia showed that the dementia incidence in both groups increased over time, while individuals with a past history of scrub typhus had a higher incidence of dementia than the control group. Second, the risk of Alzheimer’s disease was significantly higher among patients with a history of scrub typhus (adjusted hazard ratio, 1.15; 95% confidence interval 1.13–1.18, p < 0.001).

Conclusion

In conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer’s disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.
Adopting international recommendations to design a model for maternal health service to cope with pandemic disruption for Indonesian primary care
Authors: Ekawati Fitriana Murriya , Muchlis Mumtihana , Tuteja Amita
Published: March 2023

Background

Limited evidence is available as the reference for the model of care on providing maternity care in low-and-middle-income countries (LMICs) to cope with pandemic disruption. This study aimed to adopt international recommendations to develop the model of care with the context of Indonesian settings.

Methods

Four codesign workshops and substitute interviews with stakeholders, covering the (i) exploration of service provision during the pandemic, (ii) adoption of international recommendations, (iii) designing and (iv) finalising model of care for maternal health services in primary care under the COVID-19 pandemic. The study took place in Yogyakarta Province Indonesia from July-November 2021. The participants were general practitioners, midwives, nurses, patients, and obstetricians. The data were analysed thematically.

Results

Twenty-three participants were recruited. As many as 23, 16, 14 and 16 participants participated in the first to fourth codesign workshops or substitute interviews. Key recommendations agreed upon in the workshop were health screening, maintaining antenatal-postnatal breastfeeding care, limiting visitors, using telemedicine, and creating a multidisciplinary team to provide the care. A model of care for improving maternal service was also agreed and received suggestions from the participants. Identified barriers to the recommendation implementation, such as the available clinical resources and negotiating providers’ authority in practice.

Conclusion

Recommendations and the model of care for improving maternity care in Indonesia are beneficial to be implemented in Indonesian primary care during the COVID-19 pandemic. Further research includes pilot studies to explore the acceptability of the model and recommendation implementation in practice.
Psychiatric symptoms in a female with subacute combined degeneration of the spinal cord (SCD): a case report
Authors: Zhang Yinlin , Luo Huirong , Wang Xueqian , Qiu Haitang , Ren Hao , Zheng Anhai , Luo Qinghua
Published: March 2023

Background

Subacute combined degeneration of the spinal cord (SCD) is mainly caused by deficiency of Vitamin B12 and characterized by deep hypoesthesia, sensory ataxia and spasmodic paralysis of lower limbs. SCD often accompanies with megaloblastic anemia. Psychiatric symptoms could be the initial manifestations of SCD by lack of Vitamin B12, but are rarely considered secondary to physical discomfort and psychological factors in SCD. Additionally, treatment experience for psychiatric symptoms in SCD remains little reported.

Case report

We presented a case of a 37-year-old female who complained of being persecuted and controlled for one week and thus was admitted to the psychiatry department. Before that, she had went through persistent paresthesia and numbness of her lower extremities for two-month. Low Vitamin B12 level and hemoglobin concentration, neurologic symptoms and bone marrow smear results supported the clinical diagnosis of SCD and megaloblastic anemia. With supplementation of Vitamin B12 and blood transfusion and short-term prescription of antipsychotics and antidepressants, physical symptoms were improved and psychological symptoms disappeared within 2 weeks.

Conclusions

Psychiatric symptoms of SCD could be generated from lack of Vitamin B12, anemia and neurologic symptoms, where short-term use of antipsychotics and antidepressants may be effective.
Measuring social desirability bias in a multi-ethnic cohort sample: its relationship with self-reported physical activity, dietary habits, and factor structure
Authors: Teh Wen Lin , Abdin Edimansyah , P.V. Asharani , Siva Kumar Fiona Devi , Roystonn Kumarasan , Wang Peizhi , Shafie Saleha , Chang Sherilyn , Jeyagurunathan Anitha , Vaingankar Janhavi Ajit , Sum Chee Fang , Lee Eng Sing , van Dam Rob M. , Subramaniam Mythily
Published: March 2023

Background

Social desirability bias is one of the oldest forms of response bias studied in social sciences. While individuals may feel the need to fake good or bad answers in response to sensitive or intrusive questions, it remains unclear how rampant such a bias is in epidemiological research pertaining to self-reported lifestyle indicators in a multicultural Asian context. The main purpose of the current study is, therefore, to examine the sociodemographic correlates and impact of social desirability responding on self-reported physical activity and dietary habits at an epidemiological scale in a non-western multi-cultural Asian setting.

Methods

Prior to the main analyses, confirmatory and exploratory factor analyses were conducted to determine the factorial validity of a western derived concept of social desirability. Multiple regression analyses were conducted on cross-sectional data (n = 2995) extracted from a nationwide survey conducted between 2019 and 2020.

Results

A unique factor structure of social desirability was found and was therefore used for subsequent analyses. Multiple regression analyses revealed older age groups, the Indian ethnic group, those with past or present marriages, and having no income, had a significantly greater tendency to act on the bias.

Conclusion

The construct of social desirability bias was fundamentally different in a multicultural context than previously understood. Only a small proportion of variance of self-report lifestyle scores was explained by social desirability, thus providing support for data integrity.
Evaluation and guide for embedding opioid use disorder education in health professions’ curricula
Authors: Salvador Julie G. , Bolaños-Sacoman Sindy L. , Katzman Joanna G. , Morrison Ann E. , Fox Lindsay E. , Schneider Jennifer S. , Bhatt Snehal R. , Kincaid Tyler W. , Waldorf V. Ann
Published: March 2023

Background

Morbidity and mortality from Opioid Use Disorder is a health crisis in the United States. During the COVID-19 pandemic, there was a devastating increase of 38.4% in overdose deaths from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020, primarily driven by synthetic opioids. Buprenorphine is an effective medication for opioid use disorder but uptake is slow due in part to lack of provider knowledge, confidence, and negative attitudes/stigma toward patients with OUD. Addressing these barriers in academic training is a promising approach to building workforce able to effectively treat opioid use disorder.

Methods

Our university developed a training for pre-licensure physicians, physician assistants and psychiatric nurse practitioners that included the DATA Waiver training and a shadowing experience. Expected outcomes included improved knowledge, skills and attitudes about persons with OUD and buprenorphine treatment, plans to provide this treatment post-graduation, for pre-licensure learners to have completed all requirements to prescribe buprenorphine post-graduation, and for the training to be embedded into school’s curricula.

Results

Results were positive overall including improved knowledge and attitudes toward persons with OUD, better understanding of the benefits of this treatment for patients, increased confidence and motivation to provide this treatment post-graduation. The training is now embedded in each program’s graduation requirements.

Conclusion

Developing a didactic and experiential training on buprenorphine treatment for opioid use disorder and embedding it into medical, physician assistant, and psychiatric nurse practitioner licensure programs can help prepare future providers to treat opioid use disorder in a range of settings. Key to replicating this program in other university settings is to engage faculty members who actively provide treatment to persons with OUD to ensure shadowing opportunities and serve as role models for learners.
Barriers to help-seeking for Malaysian women with symptoms of breast cancer: a mixed-methods, two-step cluster analysis
Authors: Rajaram Nadia , Jaganathan Maheswari , Muniandy Kavitha , Rajoo Yamuna , Zainal Hani , Rahim Norlia , Tajudeen Nurul Ain , Zainal Nur Hidayati , Mohd Khairy Azuddin , Abdul Wahab Mohamed Yusof , Teo Soo Hwang
Published: March 2023

Background

Improving help-seeking behaviour is a key component of down-staging breast cancer and improving survival, but the specific challenges faced by low-income women in an Asian setting remain poorly characterized. Here, we determined the extent of help-seeking delay among Malaysian breast cancer patients who presented at late stages and explored sub-groups of women who may face specific barriers.

Methods

Time to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks.

Results

The average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p < 0.001). The most reported barrier across clusters was poor knowledge about breast health or breast cancer symptoms (36.3%), regardless of help-seeking behaviour (p = 0.931). Unexpectedly, women with no delay (9 days average) and great delay (259 days average) were more similar to each other than to women with mild delays (58 days average), but, women who experienced great delay reported poor motivation due to fear and embarrassment (p = 0.066) and a lack of social support (p = 0.374) to seek help.

Conclusions

Down-staging of breast cancer in Malaysia will require a multi-pronged approach aimed at modifying culturally specific social and emotional barriers, eliminating misinformation, and instilling motivation to seek help for breast health for the women most vulnerable to help-seeking delays.
m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion
Authors: Cao Xiaoxue , Geng Qishun , Fan Danping , Wang Qiong , Wang Xing , Zhang Mengxiao , Zhao Lu , Jiao Yi , Deng Tingting , Liu Honglin , Zhou Jing , Jia Liqun , Xiao Cheng
Published: March 2023

N6-methyladenosine (m6A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m6A writers, erasers, and readers, m6A modulation is involved in myriad physiological and pathological processes. Extensive studies have demonstrated m6A modulation in diverse tumours, with effects on tumorigenesis, metastasis, and resistance. Recent evidence has revealed an emerging role of m6A modulation in tumour immunoregulation, and divergent m6A methylation patterns have been revealed in the tumour microenvironment. To depict the regulatory role of m6A methylation in the tumour immune microenvironment (TIME) and its effect on immune evasion, this review focuses on the TIME, which is characterized by hypoxia, metabolic reprogramming, acidity, and immunosuppression, and outlines the m6A-regulated TIME and immune evasion under divergent stimuli. Furthermore, m6A modulation patterns in anti-tumour immune cells are summarized.
Excess healthcare costs of mental disorders in children, adolescents and young adults in the Basque population registry adjusted for socioeconomic status and sex
Authors: Larrañaga Igor , Ibarrondo Oliver , Mar-Barrutia Lorea , Soto-Gordoa Myriam , Mar Javier
Published: March 2023

Background

Mental illnesses account for a considerable proportion of the global burden of disease. Economic evaluation of public policies and interventions aimed at mental health is crucial to inform decisions and improve the provision of healthcare services, but experts highlight that nowadays the cost implications of mental illness are not properly quantified. The objective was to measure the costs of excess use of all healthcare services by 1- to 30-year-olds in the Basque population as a function of whether or not they had a mental disorder diagnosis.

Methods

A real-world data study was used to identify diagnoses of mental disorders and to measure resource use in the Basque Health Service Registry in 2018. Diagnoses were aggregated into eight diagnostic clusters: anxiety, attention deficit hyperactivity disorder, conduct disorders, mood disorders, substance use, psychosis and personality disorders, eating disorders, and self-harm. We calculated the costs incurred by each individual by multiplying the resource use by the unit costs. Annual costs for each cluster were compared with those for individuals with no diagnosed mental disorders through entropy balancing and two-part models which adjusted for socioeconomic status (SES).

Results

Of the 609,381 individuals included, 96,671 (15.9%) had ≥ 1 mental disorder diagnosis. The annual cost per person was two-fold higher in the group diagnosed with mental disorders (€699.7) than that with no diagnoses (€274.6). For all clusters, annual excess costs associated with mental disorders were significant. The adjustment also evidenced a social gradient in healthcare costs, individuals with lower SES consuming more resources than those with medium and higher SES across all clusters. Nonetheless, the effect of being diagnosed with a mental disorder had a greater impact on the mean and excess costs than SES.

Conclusions

Results were consistent in showing that young people with mental disorders place a greater burden on healthcare services. Excess costs were higher for severe mental disorders like self-harm and psychoses, and lower SES individuals incurred, overall, more than twice the costs per person with no diagnoses. A socioeconomic gradient was notable, excess costs being higher in low SES individuals than those with a high-to-medium SES. Differences by sex were also statistically significant but their sizes were smaller than those related to SES.
How do 24-h movement behaviours change during and after vacation? A cohort study
Authors: Ferguson Ty , Curtis Rachel , Fraysse Francois , Olds Timothy , Dumuid Dorothea , Brown Wendy , Esterman Adrian , Maher Carol
Published: March 2023

Background

For adults, vacations represent a break from daily responsibilities of work – offering the opportunity to re-distribute time between sleep, sedentary behaviour, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) across the 24-h day. To date, there has been minimal research into how activity behaviour patterns change on vacation, and whether any changes linger after the vacation. This study examined how daily movement behaviours change from before, to during and after vacations, and whether these varied based on the type of vacation and vacation duration.

Methods

Data collected during the Annual Rhythms In Adults’ lifestyle and health (ARIA) study were used. 308 adults (mean age 40.4 years, SD 5.6) wore Fitbit Charge 3 fitness trackers 24 h a day for 13 months. Minute-by-minute movement behaviour data were aggregated into daily totals. Multi-level mixed-effects linear regressions were used to compare movement behaviours during and post-vacation (4 weeks) to pre-vacation levels (14 days), and to examine the associations with vacation type and duration.

Results

Participants took an average of 2.6 (SD = 1.7) vacations of 12 (SD = 14) days’ (N = 9778 days) duration. The most common vacation type was outdoor recreation (35%) followed by family/social events (31%), rest (17%) and non-leisure (17%).

Daily sleep, LPA and MVPA all increased (+ 21 min [95% CI = 19,24] p < 0.001, + 3 min [95% CI = 0.4,5] p < 0.02, and + 5 min [95% CI = 3,6] p < 0.001 respectively) and sedentary behaviour decreased (-29 min [95% CI = -32,-25] p < 0.001) during vacation. Post-vacation, sleep remained elevated for two weeks; MVPA returned to pre-vacation levels; and LPA and sedentary behaviour over-corrected, with LPA significantly lower for 4 weeks, and sedentary behaviour significantly higher for one week. The largest changes were seen for “rest” and “outdoor” vacations. The magnitude of changes was smallest for short vacations (< 3 days).

Conclusions

Vacations are associated with favourable changes in daily movement behaviours. These data provide preliminary evidence of the health benefits of vacations.

Trial registration

The study was prospectively registered on the Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12619001430123).
Clinical significance of the anteromedial talus osteophyte in anteromedial ankle impingement in chronic lateral ankle instability
Authors: Zhang Jieyuan , Li Xueqian , Fu Shaoling , Yang Kai , Shi Zhongmin
Published: March 2023

Purpose

The aim of this study was to evaluate the relation between anteromedial ankle osteophytes (AMAO) and anteromedial ankle impingement (AMAI) in chronic lateral ankle instability (CLAI) through visualization and quantification.

Methods

Forty-three patients with unilateral CLAI between September 2018 and March 2020 accepted arthroscopic repair of an anterior talofibular ligament (ATFL) and were split into two groups: AMAI (AMAI including intraoperative AMAO resection) and pure CLAI (with AMAO but without AMAI, no AMAO resection). The AMAO protrusion lengths in each direction were measured and compared after all of the ankles were reconstructed. All patients were assessed preoperatively and at 2-year follow-up with ankle dorsiflexion, the American Orthopedic Foot and Ankle Society (AOFAS) ankle–hindfoot score, and visual analog scale (VAS) score.

Results

Intelligent analysis showed that a large extent of osteophytes was found at the dorsomedial surface of the talar neck in AMAI group. The upper and inner bound protrusion distances of AMAO in AMAI group were greater than in the pure CLAI group. There was no significant difference in anterior bound protrusion distance of AMAO between the two groups. Preoperatively, the ankle dorsiflexion of AMAI group (7.6 ± 1.4°) was considerably lower than that of pure CLAI group (22.4 ± 1.9°) (p < 0.001). When compared to the pure CLAI group, the AMAI group had a substantially worse AOFAS score (62.2 ± 6.7 vs 71.1 ± 9.1;p < 0.001) and VAS score (6.0 ± 1.0 vs 4.9 ± 0.8;p < 0.05). However, there was no significant difference in postoperative ankle dorsiflexion, AOFAS score, or VAS score between the two groups.

Conclusion

AMAO is formed mostly on the dorsomedial surface of the talar neck in CLAI with AMAI, and the upper and inner bound protrusion lengths of AMAO were shown to be significantly correlated with the existence of AMAI in CLAI.

Level of evidence IV.
L-kynurenine induces NK cell loss in gastric cancer microenvironment via promoting ferroptosis
Authors: Cui Jian-Xin , Xu Xian-Hui , He Tao , Liu Jia-Jia , Xie Tian-Yu , Tian Wen , Liu Jun-Yan
Published: March 2023

Background

Natural killer (NK) cells play a major role in body’s fighting against various types of cancers. Their infiltration in the tumor microenvironment (TME) of gastric cancer (GC) are significantly decreased, which has been reported as a robust prognostic marker. However, the causes leading to NK cells loss in GC TME remains poorly understood.

Methods

We constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. Then through using the specific inhibitors for different types of cell death and examining the surrogate markers, we confirmed ferroptosis in NK cells. Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells.

Results

We found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC.

Conclusions

Our study revealed a novel mechanism to explain the decline of NK cell number in GC TME. Notably, we also developed a potential immunotherapy strategy, which might be beneficial in clinical treatment in the future.
The pipeline for drugs for control and elimination of neglected tropical diseases: 1. Anti-infective drugs for regulatory registration
Authors: Pfarr Kenneth M. , Krome Anna K. , Al-Obaidi Issraa , Batchelor Hannah , Vaillant Michel , Hoerauf Achim , Opoku Nicholas O. , Kuesel Annette C.
Published: March 2023

The World Health Organization ‘Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021–2030’ outlines the targets for control and elimination of neglected tropical diseases (NTDs). New drugs are needed to achieve some of them. We are providing an overview of the pipeline for new anti-infective drugs for regulatory registration and steps to effective use for NTD control and elimination. Considering drugs approved for an NTD by at least one stringent regulatory authority: fexinidazole, included in WHO guidelines for Trypanosoma brucei gambiense African trypanosomiasis, is in development for Chagas disease. Moxidectin, registered in 2018 for treatment of individuals ≥ 12 years old with onchocerciasis, is undergoing studies to extend the indication to 4–11-year-old children and obtain additional data to inform WHO and endemic countries' decisions on moxidectin inclusion in guidelines and policies. Moxidectin is also being evaluated for other NTDs. Considering drugs in at least Phase 2 clinical development, a submission is being prepared for registration of acoziborole as an oral treatment for first and second stage T.b. gambiense African trypanosomiasis. Bedaquiline, registered for tuberculosis, is being evaluated for multibacillary leprosy. Phase 2 studies of emodepside and flubentylosin in O. volvulus-infected individuals are ongoing; studies for Trichuris trichuria and hookworm are planned. A trial of fosravuconazole in Madurella mycetomatis-infected patients is ongoing. JNJ-64281802 is undergoing Phase 2 trials for reducing dengue viral load. Studies are ongoing or planned to evaluate oxantel pamoate for onchocerciasis and soil-transmitted helminths, including Trichuris, and oxfendazole for onchocerciasis, Fasciola hepatica, Taenia solium cysticercosis, Echinococcus granulosus and soil-transmitted helminths, including Trichuris. Additional steps from first registration to effective use for NTD control and elimination include country registrations, possibly additional studies to inform WHO guidelines and country policies, and implementation research to address barriers to effective use of new drugs. Relative to the number of people suffering from NTDs, the pipeline is small. Close collaboration and exchange of experience among all stakeholders developing drugs for NTDs may increase the probability that the current pipeline will translate into new drugs effectively implemented in affected countries.

Graphical Abstract
Tofacitinib for the treatment of inflammatory bowel disease-associated arthritis: two case reports
Authors: Momen Majumder Muhammad Shoaib , Haq Syed Atiqul , Rasker Johannes J.
Published: March 2023

Background

Musculoskeletal manifestations are common extraintestinal manifestations of inflammatory bowel disease. Tofacitinib is a Janus kinase inhibitor approved for treating rheumatoid arthritis and ulcerative colitis. There are limited data on the efficacy of tofacitinib in managing inflammatory bowel disease-associated arthritis. Here we report two patients with ulcerative colitis- and Crohn’s disease-associated arthritis successfully responding to tofacitinib.

Cases

A 34-year-old Bangladeshi woman presented with lower limb polyarthritis for 7 years. Six months after the onset of polyarthritis, she developed abdominal pain with rectal bleeding. Colonoscopy and rectal biopsy findings confirmed ulcerative colitis. Ulcerative colitis associated arthritis was diagnosed. Treatment with sulfasalazine, etanercept, adalimumab, infliximab, and methotrexate gave no long-lasting remission. Methotrexate with mesalazine gave a partial response, and tofacitinib 5 mg twice per day was added. Her articular and abdominal symptoms improved within a month, and remission persisted till 24 months of follow-up, except a short-lasting mild flare at the seventh month. A 52-year-old Bangladeshi man had Crohn’s disease for 5 years. He presented with a swollen left knee and pain in other joints. Laboratory showed positive HLA-B27. He was intolerant to sulfasalazine and experienced poor response to methotrexate. Due to his inability to afford anti-tumor necrosis factor, tofacitinib was initiated. His arthritis improved within a month, and he remained in remission up to the sixth month.

Conclusions

In a woman with ulcerative colitis associated arthritis, refractory to biologic therapy, both arthritis and colitis improved with tofacitinib. A patient with Crohn’s disease-associated arthritis went into remission with tofacitinib. Tofacitinib may be effective in inflammatory bowel disease-associated arthritis.
Suburban pastoralists: Pastoral adaptation strategies at the rural-urban interface in Nairobi, Kenya
Authors: Rotich Sylvia Jemutai , Funder Mikkel , Marani Martin
Published: March 2023

How does urban expansion interact with pastoral climate change adaptation? This article explores pastoral adaptation strategies at the rural-urban interface. It examines how Maasai pastoralists in peri-urban Nairobi, Kenya, respond to climate hazards in the context of urban expansion, land use change, and land privatisation. Using mixed-method research, the study is informed by a household survey (n = 72), 38 qualitative interviews, and 12 focus group discussions. Drawing on the literature on climate change adaptation, pastoral change, and peri-urban dynamics, we find that while urban expansion provides significant challenges for pastoral livelihoods in the study area, pastoralists also engage new opportunities in the peri-urban context and employ them in their adaptation strategies. We show how adaptation strategies related to mobility, diversification, market exchange, and storage are employed through a variety of efforts including engagement with urban land markets and demand for livestock products, and by capitalising on proximity to transport, trading facilities, water, and commercial fodder. Communal pooling, another adaptation strategy, is less used and perceived to be in decline. We further find that historical land ownership patterns play a significant role in adaptation strategies, as pastoralists who have benefitted from rangeland privatisation are able to convert high peri-urban land values into private rural land access and investments in, e.g. diversification. Poor households are in a more precarious position but draw on informal agreements to access land as part of their adaptation strategies. Our findings highlight how pastoral households at the rural-urban interface may draw actively on peri-urban opportunities in their adaptation strategies as part of their efforts to enhance livelihoods, and in so doing bridge peri-urban and rural space. More broadly, our study highlights the importance of understanding pastoral climate change adaptation in the context of wider changes in livelihoods, land use, and land rights, rather than as isolated actions.

Graphical Abstract
Formation of singularity of solution to a nonlinear shallow water equation
Authors: Ming Sen , Du Jiayi , Ma Yaxian , Su Yeqin
Published: March 2023

This paper is mainly concerned with behaviors of solution to the Cauchy problem for a generalized shallow water equation with dispersive term and dissipative term in the Besov space. It is shown that the problem of nonlinear shallow water equation is locally well posed. The $H^{1}(\mathbb{R})$

H
1

(
R
)
norm of solution to the problem is bounded under certain assumption on the initial value. Several blow-up criteria of solution are presented. The solution has compact support provided that the initial value has compact support. More specifically, the solution exponentially decays at infinity if the initial value exponentially decays at infinity. Our main new contribution is that the effects of coefficients λ and β on solution are illustrated. To the best of our knowledge, the results in Theorems 1.1–1.7 are new.
Comparative analysis of different response criteria at early phase after PD-1 blockade in non-small lung cancer
Authors: Kaira Kyoichi , Yamaguchi Ou , Naruse Ichiro , Umeda Yukihiro , Honda Takeshi , Watanabe Satoshi , Ichikawa Kosuke , Yanagisawa Shin , Kasahara Norimitsu , Higuchi Tetsuya , Hashimoto Kosuke , Miura Yu , Shiono Ayako , Mouri Atsuto , Imai Hisao , Iizuka Kunihiko , Ishizuka Tamotsu , Minato Koichi , Suda Satoshi , Kagamu Hiroshi , Mori Keita , Seki Nobuhiko , Kuji Ichiei
Published: March 2023

Purpose

To compare different response criteria using computed tomography (CT) and positron emission tomography (PET) in measuring response and survival in the early phase after programmed death-1 (PD-1) blockade monotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods

A total of 54 patients with advanced NSCLC who had 2-deoxy-2-[fluorine-18]-fluoro-D-glucose PET or CT at baseline, and 4 and 9 weeks after PD-1 blockade, were registered. Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), the immune-modified RECIST (irRECIST), the PET Response Criteria in Solid Tumors (PERCIST), the immune-modified PERCIST (iPERCIST), and the European Organization for Research and Treatment of Cancer (EORTC) criteria for dichotomous groups, such as responders vs. non-responders and controlled vs. uncontrolled diseases. Cohen’s κ was used to evaluate the concordance among the different criteria.

Results

The concordance between CT and PET response criteria was fair or slight for responders vs. non-responders, but the agreement between iPERCIST and irRECIST was moderate for controlled vs. uncontrolled diseases. The agreement between EORTC and PERCIST or iPERCIST in detecting responders was higher in the application of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than in the standardized uptake value corrected for lean body mass (SUL)peak. To distinguish controlled from uncontrolled disease, RECIST, irRECIST, and PET criteria (PERCIST, iPERCIST, and EORTC) defined by MTV or TLG were found to be significant predictors of progression-free survival. To distinguish responders from non-responders, iPERCIST by SULpeak or EORTC by TLG were identified as significant indicators. The EORTC criteria using TLG for the detection of responders or uncontrolled diseases had a significantly higher predictive value for response assessment.

Conclusions

The EORTC criteria based on TLG for the early detection of responders and uncontrolled disease were effective as a response assessment at 4 weeks after the PD-1 blockade. When SULpeak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect.
Appropriate feeding practice and associated factors among under-five children with diarrheal disease in sub-Saharan Africa: a multi-country analysis
Authors: Yeshaw Yigizie , Alem Adugnaw Zeleke , Ayalew Hiwotie Getaneh , Liyew Alemneh Mekuriaw , Tessema Zemenu Tadesse , Worku Misganaw Gebrie , Tesema Getayeneh Antehunegn , Alamneh Tesfa Sewunet , Teshale Achamyeleh Birhanu
Published: March 2023

Background

Diarrheal disease is one of the leading causes of child mortality and morbidity in low-income countries. Although the provision of more fluid and solid foods during diarrhea are important to treat the diseases, in Africa, food and fluid restrictions are common during diarrheal illness. Therefore, the aim of this study was to determine appropriate feeding practice and associated factors among under-five children with diarrheal disease in sub-Saharan Africa (SSA).

Methods

We have used the appended most recent demographic and health survey (DHS) datasets of 35 sub-Saharan countries conducted from 2010 to 2020. A total weighted sample of 42,882 living children with diarrhea were included in the analyses. Multivariable multilevel binary logistic regression was used to identify factors associated with appropriate child feeding practice in SSA. A p value of ≤ 0.05 was used as a cut of point to declare statistically significant variables.

Results

The overall prevalence of appropriate child feeding practice in this study was 10.45% (95% CI 10.17–10.74). The odds of having appropriate child feeding practice was higher among women with primary (AOR = 1.27: 1.17–1.37), secondary (AOR = 1.38: 1.25–1.52), and higher education level (AOR = 1.52: 1.21–1.90), media exposure (AOR = 1.11: 1.11–1.29), richer (AOR = 1.23:1.01–1.26) and richest (AOR = 1.19:1.05–1.35) wealth index, and currently working (AOR = 1.12: 1.04–1.19).

Conclusion

The prevalence of appropriate child feeding practice in this study was found to be very low. It advisable to reduce diarrhea-related child mortality through enhancing diarrhea management practice especially by working on the after mentioned factors.
Crosscorrelation-based Marchenko imaging with an optimal aperture
Authors: Chen Xiaochun , Hu Yezheng , Wo Yukai , Huang Xuri , Yue Yubo , Cao Weiping , Chen Kang
Published: March 2023

The Marchenko method can retrieve Green’s functions among virtual sources in the subsurface and receivers at the surface from single-sided reflection data. This process, called Marchenko redatuming, allows the estimation of the full-wavefield information in the inhomogeneous subsurface. The retrieved Green’s functions form the input for creating the subsurface image free of artifacts caused by internal multiples. However, when using the crosscorrelation imaging condition in Marchenko imaging, the shallower regions of the obtained image suffer from reduced resolution due to unwanted interference, which occurs in the crosscorrelation gathers at far offsets. With a simple model, we have found that the image resolution obtained using the crosscorrelation Marchenko imaging (CCMI) method is influenced by image position and the integral range of the crosscorrelation function. To overcome this problem, we develop an optimal aperture-bounded crosscorrelation imaging condition using only the constructive wavefields during integration. The optimal aperture is defined as an intercept at which the time difference between the first arrivals of up- and downgoing Green’s functions equals one wavelet period. The integration of the crosscorrelation function is then performed over the determined optimal range that varies with the image position rather than a fixed aperture. As a result, we exclude the unwanted destructive interference from the crosscorrelation gather, resulting in a high-resolution image. The effectiveness of our method has been validated with its applications to synthetic and field data tests.
Is 3D frequency-domain FWI of full-azimuth/long-offset OBN data feasible? The Gorgon data FWI case study
Authors: Operto S. , Amestoy P. , Aghamiry H. , Beller S. , Buttari A. , Combe L. , Dolean V. , Gerest M. , Guo G. , Jolivet P. , L'Excellent J.-Y. , Mamfoumbi F. , Mary T. , Puglisi C. , Ribodetti A. , Tournier P.-H.
Published: March 2023

Frequency-domain full-waveform inversion (FWI) is potentially amenable to efficient processing of full-azimuth long-offset stationary-recording seabed acquisition carried out with a sparse layout of ocean-bottom nodes (OBNs) and broadband sources because the inversion can be performed with a few discrete frequencies. However, computing the solution of the forward (boundary-value) problem efficiently in the frequency domain with linear algebra solvers remains a challenge for large computational domains involving tens to hundreds of millions of parameters. We illustrate the feasibility of 3D frequency-domain FWI with a subset of the 2015/2016 Gorgon OBN data set in the North West Shelf, Australia. We solve the forward problem with the massively parallel multifrontal direct solver MUMPS, which includes four key features to reach high computational efficiency: an efficient parallelism combining message-passing interface and multithreading, block low-rank compression, mixed-precision arithmetic, and efficient processing of sparse sources. The Gorgon subdata set involves 650 OBNs that are processed as reciprocal sources and 400,000 sources. Monoparameter FWI for vertical wavespeed is performed in the viscoacoustic vertically transverse isotropic approximation with a classical frequency continuation approach proceeding from a starting frequency of 1.7 Hz to a final frequency of 13 Hz. The target covers an area ranging from 260 km2 (frequency ≥ 8.5 Hz) to 705 km2 (frequency ≤ 8.5 Hz) for a maximum depth of 8 km. Compared to the starting model, FWI dramatically improves the reconstruction of the bounding faults of the Gorgon horst at reservoir depths as well as several intrahorst faults and several horizons of the Mungaroo Formation down to a depth of 7 km. Seismic modeling reveals a good kinematic agreement between recorded and simulated data, but amplitude mismatches between the recorded and simulated reflection from the reservoir suggest elastic effects. Therefore, future works involve multiparameter reconstruction for density and attenuation before considering elastic FWI from hydrophone and geophone data.