bluuebunny/crossref_metadata_2025 huggingface dataset:
Unearthing a novel function of SRSF1 in binding and unfolding of RNA G-quadruplexes
Authors: De Silva Naiduwadura Ivon Upekala , Lehman Nathan , Fargason Talia , Paul Trenton , Zhang Zihan , Zhang Jun
Published: April 2024

SRSF1 governs splicing of over 1500 mRNA transcripts. SRSF1 contains two RNA-recognition motifs (RRMs) and a C-terminal Arg/Ser-rich region (RS). It has been thought that SRSF1 RRMs exclusively recognize single-stranded exonic splicing enhancers, while RS lacks RNA-binding specificity. With our success in solving the insolubility problem of SRSF1, we can explore the unknown RNA-binding landscape of SRSF1. We find that SRSF1 RS prefers purine over pyrimidine. Moreover, SRSF1 binds to the G-quadruplex (GQ) from the ARPC2 mRNA, with both RRMs and RS being crucial. Our binding assays show that the traditional RNA-binding sites on the RRM tandem and the Arg in RS are responsible for GQ binding. Interestingly, our FRET and circular dichroism data reveal that SRSF1 unfolds the ARPC2 GQ, with RS leading unfolding and RRMs aiding. Our saturation transfer difference NMR results discover that Arg residues in SRSF1 RS interact with the guanine base but not other nucleobases, underscoring the uniqueness of the Arg/guanine interaction. Our luciferase assays confirm that SRSF1 can alleviate the inhibitory effect of GQ on gene expression in the cell. Given the prevalence of RNA GQ and SR proteins, our findings unveil unexplored SR protein functions with broad implications in RNA splicing and translation.
Multiplexed in-situ mutagenesis driven by a dCas12a-based dual-function base editor
Authors: Wu Yaokang , Li Yang , Liu Yanfeng , Xiu Xiang , Liu Jiaheng , Zhang Linpei , Li Jianghua , Du Guocheng , Lv Xueqin , Chen Jian , Ledesma-Amaro Rodrigo , Liu Long
Published: April 2024

Mutagenesis driving genetic diversity is vital for understanding and engineering biological systems. However, the lack of effective methods to generate in-situ mutagenesis in multiple genomic loci combinatorially limits the study of complex biological functions. Here, we design and construct MultiduBE, a dCas12a-based multiplexed dual-function base editor, in an all-in-one plasmid for performing combinatorial in-situ mutagenesis. Two synthetic effectors, duBE-1a and duBE-2b, are created by amalgamating the functionalities of cytosine deaminase (from hAPOBEC3A or hAID*Δ ), adenine deaminase (from TadA9), and crRNA array processing (from dCas12a). Furthermore, introducing the synthetic separator Sp4 minimizes interference in the crRNA array, thereby facilitating multiplexed in-situ mutagenesis in both Escherichia coli and Bacillus subtilis. Guided by the corresponding crRNA arrays, MultiduBE is successfully employed for cell physiology reprogramming and metabolic regulation. A novel mutation conferring streptomycin resistance has been identified in B. subtilis and incorporated into the mutant strains with multiple antibiotic resistance. Moreover, surfactin and riboflavin titers of the combinatorially mutant strains improved by 42% and 15-fold, respectively, compared with the control strains with single gene mutation. Overall, MultiduBE provides a convenient and efficient way to perform multiplexed in-situ mutagenesis.
Nanoscale millefeuilles produce iridescent bill ornaments in birds
Authors: Nicolaï Michaël P J , Debruyn Gerben , Soenens Mieke , Shawkey Matthew D , D’Alba Liliana
Published: April 2024

Colors are well studied in bird plumage but not in other integumentary structures. In particular, iridescent colors from structures other than plumage are undescribed in birds. Here, we show that a multilayer of keratin and lipids is sufficient to produce the iridescent bill of Spermophaga haematina. Furthermore, that the male bill is presented to the female under different angles during display provides support for the hypothesis that iridescence evolved in response to sexual selection. This is the first report of an iridescent bill, and only the second instance of iridescence in birds in which melanosomes are not involved. Furthermore, an investigation of museum specimens of an additional 98 species, showed that this evolved once, possibly twice. These results are promising, as they suggest that birds utilize a wider array of physical phenomena to produce coloration and should further stimulate research on nonplumage integumentary colors.
On Block's delineation of the border between seeing and thinking
Authors: Hill Christopher S
Published: April 2024

This note is concerned with Ned Block's claim that cognition differs from perception in being paradigmatically conceptual, propositional, and non-iconic. As against Block, it maintains that large stretches of cognition constitutively involve, or depend on, iconic representations.
Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High Risk for Psychosis
Authors: Livingston Nicholas R , De Micheli Andrea , McCutcheon Robert A , Butler Emma , Hamdan Marwa , Grace Anthony A , McGuire Philip , Egerton Alice , Fusar-Poli Paolo , Modinos Gemma
Published: April 2024

Background and Hypothesis

Animal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences real-world clinical outcomes in individuals at clinical high risk for psychosis (CHR-P) is unknown.

Study Design

This observational cohort study used electronic health record data from CHR-P individuals to investigate whether BDZ exposure (including hypnotics, eg, zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample.

Study Results

567 CHR-P individuals (306 male, mean[±SD] age = 22.3[±4.9] years) were included after data cleaning. The BDZ-exposed (n = 105) and BDZ-unexposed (n = 462) groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HR = 1.61; 95% CI: 1.03–2.52; P = .037), psychiatric hospital admission (HR = 1.93; 95% CI: 1.13–3.29; P = .017), home visit (HR = 1.64; 95% CI: 1.18–2.28; P = .004), and Accident and Emergency department attendance (HR = 1.88; 95% CI: 1.31–2.72; P < .001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all P > .05). In an analysis restricted to antipsychotic-naïve individuals, BDZ exposure reduced the risk of transition to psychosis numerically, although this was not statistically significant (HR = 0.59; 95% CI: 0.32–1.08; P = .089).

Conclusions

BDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.
Sleep-Deep-Learner is taught sleep–wake scoring by the end-user to complete each record in their style
Authors: Katsuki Fumi , Spratt Tristan J , Brown Ritchie E , Basheer Radhika , Uygun David S
Published: April 2024

Sleep–wake scoring is a time-consuming, tedious but essential component of clinical and preclinical sleep research. Sleep scoring is even more laborious and challenging in rodents due to the smaller EEG amplitude differences between states and the rapid state transitions which necessitate scoring in shorter epochs. Although many automated rodent sleep scoring methods exist, they do not perform as well when scoring new datasets, especially those which involve changes in the EEG/EMG profile. Thus, manual scoring by expert scorers remains the gold standard. Here we take a different approach to this problem by using a neural network to accelerate the scoring of expert scorers. Sleep-Deep-Learner creates a bespoke deep convolution neural network model for individual electroencephalographic or local-field-potential (LFP) records via transfer learning of GoogLeNet, by learning from a small subset of manual scores of each EEG/LFP record as provided by the end-user. Sleep-Deep-Learner then automates scoring of the remainder of the EEG/LFP record. A novel REM sleep scoring correction procedure further enhanced accuracy. Sleep-Deep-Learner reliably scores EEG and LFP data and retains sleep–wake architecture in wild-type mice, in sleep induced by the hypnotic zolpidem, in a mouse model of Alzheimer’s disease and in a genetic knock-down study, when compared to manual scoring. Sleep-Deep-Learner reduced manual scoring time to 1/12. Since Sleep-Deep-Learner uses transfer learning on each independent recording, it is not biased by previously scored existing datasets. Thus, we find Sleep-Deep-Learner performs well when used on signals altered by a drug, disease model, or genetic modification.
Xanthomonas Strains Isolated from Hosts in the Family Araceae Reveal Diverse Phylogenetic Relationships and Origins
Authors: Chuang Shu-Cheng , Dobhal Shefali , Pal Kanak , Amore Teresita D. , Alvarez Anne M. , Arif Mohammad
Published: April 2024

The family Araceae, comprising ornamentals including Anthurium, Dieffenbachia, Philodendron, Colocasia, and Zantedeschia, is susceptible to Xanthomonas pathogens. Previous analyses have established heterogeneity in aroid strains, yet unresolved taxonomic positions and dynamics between Xanthomonas and frequently associated Stenotrophomonas in aroids necessitate in-depth genetic investigation to resolve these complex relationships. This study utilized multilocus sequence analysis of housekeeping genes atpD, dnaA, dnaK, gltA, and gyrB to investigate 59 aroid strains, selected based on hosts, time, and geographical origins. After adding sequences from additional strains from NCBI GenBank, analysis of 161 concatenated sequences indicated that all aroid strains fell within Xanthomonas and Stenotrophomonas. Thirty-six strains isolated from Anthurium grouped under X. phaseoli, with outliers including one strain each in X. arboricola and X. sacchari and two in Stenotrophomonas. Six strains from Caladium, Dieffenbachia, and Philodendron formed host-specific subgroups within X. euvesicatoria. One strain from Dieffenbachia aligned with X. campestris, whereas strains from Colocasia, Aglaonema, and Spathiphyllum clustered with X. sacchari. Apart from the zantedeschia strain described as X. arboricola pv. zantedeschiae, two colocasia, one epipremnum, and one anthurium strain joined the X. arboricola group. Overall, this study revealed significant heterogeneity among aroid strains, with anthurium strains clustering closely despite distant geographical origins. The analysis underscores the complexity of host-pathogen specificity within Xanthomonas and emphasizes the need for further taxonomic clarification through whole-genome analysis of representative strains. The findings of this research will facilitate strain selection for inclusivity and exclusivity panels in developing diagnostic assays for X. phaseoli and xanthomonads affecting aroids.
Enhanced protein‐metabolite correlation analysis: To investigate the association between Staphylococcus aureus mastitis and metabolic immune pathways
Authors: Chen Kuo , Hu Binhong , Ren Jingyuan , Deng Xin , Li Qing , Zhang Rong , Zhang Yuanyuan , Shen Gengyu , Liu Songqing , Zhang Jiacheng , Lu Pengwei
Published: April 2024

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut‐metabolism‐mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L‐isoleucine and cholic acid along with 7‐ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood–milk barrier integrity was disrupted. Analysis of protein‐metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood–milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.
Biological treatments in childhood asthma
Authors: Nieto-García Antonio , Nieto-Cid María , Mazón-Ramos Ángel
Published: April 2024

Purpose of review

The aim is to update the information currently available for the use of biologics in severe asthma in children, in order to facilitate their prescription as far as possible.

Recent findings

The appearance of biologics for the treatment of severe asthma has meant a revolutionary change in the therapeutic approach to this disease. Currently, five biologics have been approved for severe asthma in children and/or adolescents by the regulatory agencies: omalizumab, mepolizumab, benralizumab, dupilumab and tezepelumab. But despite their positive results in terms of efficacy, there are still relevant points of debate that should induce caution when selecting the most appropriate biologic in a child with severe asthma. Indeed, safety is essential and, for several of the existing treatments, the availability of medium-term to long-term data in this regard is scarce.

The use of biologics can facilitate the therapeutic paradigm shift from pleiotropic treatments to personalized medicine. However, the choice of the most appropriate biologics remains a pending issue. On the other hand, to the extent that several of the biologics have been available for a relatively short time, the most robust evidence in terms of efficacy and safety in children is that of omalizumab.
Pooled and global burdens and trends of five common cancers attributable to diet in 204 countries and territories from 1990 to 2019: an analysis of the Global Burden of Disease Study
Authors: Ding Qiang , Ma Xiaoli , Zhang Zerui , Lu Panpan , Liu Mei
Published: April 2024

Objective

Increasing evidence has shown that dietary behaviors are closely correlated with the carcinogenesis and progression of many types of cancer. However, few studies have assessed the global diet-related burden of cancer. This study aimed to estimate the pooled burdens and trends of five types of cancers attributable to dietary behaviors.

Methods

Data regarding cancer attributable to dietary behaviors were extracted from the Global Burden of Disease study 2019, including the death cases and age-standardized death rates, and disability-adjusted life years (DALYs) estimated according to diseases, age, sex, the socio-demographic index (SDI) and location.

Results

According to the Global Burden of Disease study 2019, five types of cancer were affected by dietary behaviors: colon and rectum cancer; tracheal, bronchus and lung cancer; stomach cancer; esophageal cancer and breast cancer. Unhealthy dietary behaviors for cancer caused a total of 605.4 thousand deaths and 13951.3 thousand DALYs globally. The burden of cancer attributable to dietary risks was higher for men than for women. The highest age-standardized death rates in 2019 were observed in southern Latin America, and the lowest rates were observed in North Africa and the Middle East. The greatest increases in the age-standardized death rates, from 1990 to 2019, were found in Western Sub-Saharan Africa, with the greatest decreases in Central Asia. The highest attributable proportions of death or DALYs were colon and rectum cancer. The greatest diet-related cancer burden was observed in regions with a high-middle SDI.

Conclusion

Global age-standardized deaths and DALYs rates attributable to diet-related cancer are considerable and cause a substantial burden. Successful population-wide initiatives targeting unhealthy dietary behaviors would reduce this burden.
Incidence rates of bladder and kidney cancers among US military servicemen: comparison with the rates in the general US population
Authors: Bytnar Julie A. , McGlynn Katherine A. , Kern Sean Q. , Shriver Craig D. , Zhu Kangmin
Published: April 2024

Objective

The military population may differ from the general population in factors related to bladder and kidney cancers. However, incidence rates of these cancers have not been systematically compared between the two populations. This study compared incidence rates of bladder and kidney cancers between active-duty servicemen and men in the general US population.

Methods

Data were obtained from the Department of Defense’s Automated Central Tumor Registry (ACTUR) and the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. Included were 18–59-year-old active-duty servicemen in ACTUR and men in SEER who were diagnosed with malignant bladder and kidney cancers from 1990 to 2013. Age-adjusted rates, incidence rate ratios (IRR) and their 95% confidence intervals (95% CI) were compared between the two populations by age, race, and cancer stage.

Results

Incidence rates were lower in ACTUR than SEER for bladder cancer overall (IRR = 0.55, 95% CI, 0.48–0.62) and by age (except ages 50–59), race, and tumor stage. For ages 50–59, rates did not differ between the populations. Kidney cancer incidence rates were lower in the military for younger groups and Black men, but higher for ages 50–59.

Conclusion

Lower bladder and kidney cancer incidence in ACTUR, notably in younger men, may be primarily associated with better health and healthcare access. The lack of differences in bladder or kidney cancer incidence among 50–59-year-old men between the populations might result from multifactorial effects, such as the possible effects of cumulative military-related exposures offset by healthier status and better medical care.
Validation of ICD-10 Codes for Severe Maternal Morbidity at Delivery in a Public Hospital
Authors: Boulet Sheree L. , Stanhope Kaitlyn K. , Valdez-Sinon Arielle N. , Vuncannon Danielle , Preslar Jessica , Bergbower Hannah , Gray Brendan , Gathoo Asmita , Hansen Nora , Andre Kerri , Bensouda Sabrine , Braun Cally , Platner Marissa
Published: April 2024

Background:

Severe maternal morbidity is a composite measure of serious obstetric complications that is often identified in administrative data using the International Classification of Diseases (ICD) diagnosis and procedure codes for a set of 21 indicators. Prior studies of screen-positive cases have demonstrated low predictive value for ICD codes relative to the medical record. To our knowledge, the validity of ICD-10 codes for identifying severe maternal morbidity has not been fully described.

Methods:

We estimated the sensitivity, specificity, positive predictive value, and negative predictive value of ICD-10 codes for severe maternal morbidity occurring at delivery, compared with medical record abstraction (gold standard), for 1,000 deliveries that took place during 2016–2018 at a large, public hospital.

Results:

We identified a total of 67 cases of severe maternal morbidity using the ICD-10 definition and 74 cases in the medical record. The sensitivity was 26% (95% confidence interval [CI] = 16%, 37%), the positive predictive value was 28% (95% CI = 18%, 41%), the specificity was 95% (95% CI = 93%, 96%), and the negative predictive value was 94% (95% CI = 92%, 96%).

Conclusions:

The validity of ICD-10 codes for severe maternal morbidity in our high-burden population was poor, suggesting considerable potential for bias.
If You Torture Your Data Long Enough, It Will Confess to Anything: On the Epidemiological Basis of the LNT Model
Authors: Socol Yehoshua
Published: April 2024

This note deals with epidemiological data interpretation supporting the linear no-threshold model, as opposed to emerging evidence of adaptive response and hormesis from molecular biology in vitro and animal models. Particularly, the US–Japan Radiation Effects Research Foundation’s lifespan study of atomic bomb survivors is scrutinized. We stress the years-long lag of the data processing after data gathering and evolving statistical models and methodologies across publications. The necessity of cautious interpretation of radiation epidemiology results is emphasized.
Science-informed Policy Making for Protecting People and the Environment from Radiation
Authors: Borrego David , Nagata Jonathan S. , Boyd Michael A. , DeCair Sara D. , Matakas Lauren R. , Wang Ellen W. , Pawel David J. , Ansari Armin J.
Published: April 2024

The process to arrive at the radiation protection practices of today to protect workers, patients, and the public, including sensitive populations, has been a long and deliberative one. This paper presents an overview of the US Environmental Protection Agency’s (US EPA) responsibility in protecting human health and the environment from unnecessary exposure to radiation. The origins of this responsibility can be traced back to early efforts, a century ago, to protect workers from x rays and radium. The system of radiation protection we employ today is robust and informed by the latest scientific consensus. It has helped reduce or eliminate unnecessary exposures to workers, patients, and the public while enabling the safe and beneficial uses of radiation and radioactive material in diverse areas such as energy, medicine, research, and space exploration. Periodic reviews and analyses of research on health effects of radiation by scientific bodies such as the National Academy of Sciences, National Council on Radiation Protection and Measurements, United Nations Scientific Committee on the Effects of Atomic Radiation, and the International Commission on Radiological Protection continue to inform radiation protection practices while new scientific information is gathered. As a public health agency, US EPA is keenly interested in research findings that can better elucidate the effects of exposure to low doses and low dose rates of radiation as applicable to protection of diverse populations from various sources of exposure. Professional organizations such as the Health Physics Society can provide radiation protection practitioners with continuing education programs on the state of the science and describe the key underpinnings of the system of radiological protection. Such efforts will help equip and prepare radiation protection professionals to more effectively communicate radiation health information with their stakeholders.
Meta-Analysis of Endoscopic Full-Thickness Resection Versus Endoscopic Submucosal Dissection for Complex Colorectal Lesions
Authors: Singh Sahib , Mohan Babu P. , Vinayek Rakesh , Dutta Sudhir , Dahiya Dushyant S. , Gangwani Manesh K. , Suresh Kumar Vishnu C. , Aswath Ganesh , Bhat Ishfaq , Inamdar Sumant , Sharma Neil , Adler Douglas G.
Published: April 2024

Background:

Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data.

Methods:

Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated.

Results:

A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01).

Discussion:

This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.
Craniofacial Fibrous Dysplasia: Experience at San José Hospital, Bogotá, Colombia
Authors: Cantini J. Ernesto , Vergel M. Fernanda , Tapiero Xiomara , Gómez-Ortega Viviana
Published: April 2024

Introduction:

Fibrous dysplasia is a disorder in which normal bone is gradually replaced by immature fibro-osseous tissue, with an incidence of less than 7% of all benign bone tumors. The management of this disease is a challenge for plastic surgeons and neurosurgeons.

Goal:

To describe the diagnostic, therapeutic, and outcome approach of patients with craniofacial fibrous dysplasia seen at the Plastic Surgery Service of the Hospital San José in Bogotá, Colombia.

Methods:

This is a descriptive and retrospective case series study of patients diagnosed with monostotic and polyostotic fibrous dysplasia treated at the Plastic Surgery Department of Hospital San José during the period from January 1, 2010, to July 31, 2023.

Results:

All (n=10) of the patients had monostotic craniofacial fibrous dysplasia. The most affected bones in patients with monostotic fibrous dysplasia were zone I bones (n=10, 100%), followed by zone II bones (n=2, 20%). Patients with zone I and II involvement manifested throbbing headaches associated with phosphenes and tinnitus (n=8, 80%) and pain during occlusion associated with edema in the affected cheek (n=5, 50%). Physical examination showed that patients with orbital wall involvement (zone I bone) had ocular dystopia (n=7, 70%).

Regarding the treatment received by the patients, 90% (n=9) of the patients received surgical management as primary treatment, with orbitotomy, replacement, and/or remodeling of the roof and lateral wall of the orbit with bone graft, drilling, canthoplasty, ciliary suspension being the most frequently performed procedure (n=6, 60%). Of the patients, 20% (n=2) required reintervention.

Conclusions:

FD is a slowly progressive benign fibro-osseous disease that requires a timely, individualized, and multidisciplinary diagnosis and treatment to obtain favorable clinical and surgical results.

The mainstay of treatment is surgery as a preventive measure since it is important to avoid future functional alterations that, depending on the location of the dysplasia, would cause a high risk of alteration of adjacent structures.
Postoperative Intermaxillary Elastic Traction Contributes to the Stability of Absorbable Plates Fixation for Bilateral Mandibular Fracture
Authors: Lin Yuxin , Lv Kun
Published: April 2024

The use of absorbable plates can be challenging for mandibular fractures involving bilateral dentition. Chewing and mouth opening movements may cause loosening or breakage of absorbable materials, leading to displacement of bone segments and resulting in malocclusion. The use of absorbable materials for bilateral mandibular fracture surgery itself raises concerns for surgeons. Timely intermaxillary elastic traction is essential for these patients after surgery to maintain correct occlusion. The surgical approaches were performed with intraoral mandibular sulcus incisions. During the surgery, intermaxillary fixation screws were implanted and steel wires were used for intermaxillary ligation and fixation to restore the occlusal. After the fractured segments were sequentially reduced, they were fixed with inion 2.0 absorbable plates. The patient underwent intermaxillary elastic traction for 1 week. Elastic mask was used to assist in stabilizing the position of the jawbone and maintaining occlusion. After discharge, the patient continued traction at home for 3 weeks before removing the intermaxillary fixation screws. The patient recovered well after surgery without any complications. The postoperative occlusal relationship is good. Postoperative CT showed good reduction of the fractured segments. For the case reported in this article, elastic traction was promptly implemented after surgery. We emphasize that restoring occlusion is always the treatment goal for jawbone fractures. We believe that keeping the intermaxillary fixation screws for a month is a wise choice to be prepared for unexpected needs.
Infant Oral Candidiasis and Bottle Cleaning Methods
Authors: Stoltz Patricia , Bavousett Tamara
Published: April 2024

As manufacturers produce bottles with additional parts, such as an anticolic straw, cleaning time increases. Increased cleaning time potentially decreases cleaning effectiveness and, thus, increases the chance for thrush. This study explored the relationship between the number of bottle parts and cleaning methods for bottle-fed-only infants (<13 months) presenting with oral candidiasis. After obtaining demographic information on eligible infants (via parental consent) from the chart, caregivers of 60 infants verbally completed a questionnaire. The questionnaire elicited information about the preferred bottle for feeding, number of parts, washing frequency, washing method, drying method, sterilization frequency, and sterilization method. The χ2 test, and Fisher's exact test when necessary, was performed to examine the relationship between each reported cleaning method (washing, drying, and sterilization) compared with the number of bottle parts (≤3 or ≥4). The number of bottle parts showed no association with bottle cleaning methods (p > .05). Although there were no statistically significant relationships, trends did present that warrant investigation. Future studies to confirm recommended practices for cleaning methods and identify those at risk from demographic data could positively affect the health of bottle-fed infants by reducing the occurrence of thrush.
Treatment discontinuation in older people with multiple sclerosis
Authors: Zhu Wen , Xia Zongqi
Published: April 2024

Purpose of review

The aim of this review was to examine the evidence for disease-modifying therapies (DMTs) discontinuation in older people with multiple sclerosis (MS). We first summarized aging-associated biological changes that influence MS progression and DMT effectiveness, and then summarized recent evidence in evaluating clinical outcomes of discontinuing DMTs in older people with MS.

Recent findings

Recent findings provide mixed evidence regarding the outcomes of DMT discontinuation in older people with MS. Retrospective observational studies suggested older age and longer stable duration on DMT before DMT discontinuation were associated with lower risk of relapse in people with MS. However, one randomized clinical trial did not demonstrate the noninferiority of DMT discontinuation.

The available clinical evidence examining DMT discontinuation in older people with MS remains inconclusive. More robust evidence from clinical trials and real-world data will be necessary to guide clinical decisions regarding DMT discontinuation in older people with MS.
Rest the Brain to Learn New Gait Patterns after Stroke
Authors: Krishnan Chandramouli , Augenstein Thomas E. , Claflin Edward S. , Hemsley Courtney R , Washabaugh Edward P. , Ranganathan Rajiv
Published: April 2024

Background

The ability to relearn a lost skill is critical to motor recovery after a stroke. Previous studies indicate that stroke typically affects the processes underlying motor control and execution but not the learning of those skills. However, these prior studies could have been confounded by the presence of significant motor impairments and/or have not focused on motor acuity tasks (i.e., tasks focusing on the quality of executed actions) that have direct functional relevance to rehabilitation.

Methods

Twenty-five participants (10 stroke; 15 controls) were recruited for this prospective, case-control study. Participants learned a novel foot-trajectory tracking task on two consecutive days while walking on a treadmill. On day 1, participants learned a new gait pattern by performing a task that necessitated greater hip and knee flexion during the swing phase of the gait. On day 2, participants repeated the task with their training leg to test retention. An average tracking error was computed to determine online and offline learning and was compared between stroke survivors and uninjured controls.

Results

Stroke survivors were able to improve their tracking performance on the first day (p=0.033); however, the amount of learning in stroke survivors was lower in comparison with the control group on both days (p≤0.05). Interestingly, the offline gains in motor learning were higher in stroke survivors when compared with uninjured controls (p=0.011).

Conclusions

The results suggest that even high-functioning stroke survivors may have difficulty acquiring new motor skills related to walking, which may be related to the underlying neural damage caused at the time of stroke. Furthermore, it is likely that stroke survivors may require longer training with adequate rest to acquire new motor skills, and rehabilitation programs should target motor skill learning to improve outcomes after stroke.
DeepQCT: Predicting fragility fracture from high-resolution peripheral quantitative CT using deep learning
Authors: Chen Fangyuan , Cui Lijia , Jin Qiao , Wu Yushuo , Li Jiaqi , Jiang Yan , Chi Yue , Jiajue Ruizhi , Liu Wei , Yu Wei , Pang Qianqian , Wang Ou , Li Mei , Xing Xiaoping , Zhang Xuegong , Xia Weibo
Published: April 2024

Background Osteoporosis is prevalent in elderly women, which causes fragility fracture and hence increased mortality and morbidity. Predicting osteoporotic fracture risk is both clinically-beneficial and cost-effective. However, traditional tools using clinical factors and bone mineral density (BMD) fail to reflect bone microstructure. Here we aim to use high-resolution peripheral quantitative CT (HR-pQCT) images to construct deep-learning models which predict fragility fracture history in elderly Chinese women. Methods We used ChiVOS, a community-based national cohort of 2,664 Chinese elderly women. Demographic data, BMD, and HR-pQCT from 216 patients were used to construct three groups of models: BMD, pQCT-index, and DeepQCT. For DeepQCT, we used ResNet34 as classifier, and logistic regression for late fusion. Models were developed using 6-fold cross-validation in development set (90%, N=195), and tested in internal test set (10%, N=21). We applied unsupervised clustering on HR-pQCT indices to derive patient subgroups. Findings DeepQCT (best model AUC 0.86-0.94) was superior or similar to pQCT-index (best model AUC 0.8-0.93), which both outperformed BMD (best model AUC 0.54-0.78). Surprisingly, DeepQCT built from non-weight-bearing bones performed similarly to weight-bearing bones. Furthermore, two distinct patient groups were classified using HR-pQCT indices. The one with higher DeepQCT risk score showed lower volumetric BMD, bone more microarchitectural abnormalities, and had higher probability of osteoporosis and fragility fracture history. Interpretation DeepQCT scores and HR-pQCT-index permit early recognition of patients with high risk of fragility fracture. This established framework can be easily adapted for other diagnostic tasks using HR-pQCT scans, which promotes bone health management via digital medicine.
Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process
Authors: Zhang Cangang , Ren Tao , Zhao Xiaofan , Su Yanhong , Wang Qianhao , Zhang Tianzhe , He Boxiao , Wu Ling-Yun , Sun Lina , Zhang Baojun , Xia Zheng
Published: April 2024

The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas CD4_CTL precursors were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift-myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model, PHARE (https://xiazlab.org/phare/), which applies to both scRNA-seq and bulk RNA-seq data. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.
Population growth poses a significant threat to forest ecosystems: a case study from the Hindukush-Himalayas of Pakistan
Authors: Alam Naveed , Ullah Zahid , Ahmad Bilal , Ali Ahmad , Syed Kashmala
Published: April 2024

Human population growth and associated increases in anthropogenic activities pose a significant threat to forest ecosystems by diminishing the natural ecosystem services these systems provide. Malam Jabba is located in District Swat Pakistan’s Hindukush-Himalayan temperate zone, which is renowned for ecotourism and skiing and is rich in timber-producing tree species, medicinal plants, and unique biodiversity; however, the majority of Swat Valley’s population relies on Malam Jabba forests for their timber & fuelwood requirements. We examined how the deforestation rate increased with increasing human population density in Pakistan’s Malam Jabba area of the Hindukush-Himalayas. To identify the forest cover, remote sensing, and geographic information systems were used (RS & GIS). The study area’s vegetation was analyzed with the Normalized Divergence Vegetation Index (NDVI) using multitemporal satellite images for the years 1980, 2000, and 2020. The deforestation rate from 1980 to 2020 was then determined using the decay model, and the MATLAB program was used to predict the deforestation rate for the following two decades in relation to the anticipated growth in the human population. Our result revealed that, in the last two decades, the average rate of deforestation increased from 0.7% to 1.93% per year, while the human population of District Swat increased from 1.2 to 2.3 million at a rate of 9% per year. The decay model predicts that the study area’s deforestation rate will increase to 2.5% per year over the next two decades due to the forecasted 11.6% per year population growth rate. Human population growth in District Swat, Pakistan has seriously threatened the nearby forest ecosystems, and a future increase in human population will further accelerate anthropogenic activities like unsustanible tourism, fuel and timber wood collection and urbanization. Based on our results, we recommend that: (i) in addition to reforestation programs and sustainable use of forest resources, the government should implement a long-term forest management plan (ii) where the density of forest cover can be sustained at an equilibrium level dependent of population growth pressure (iii) and areas with extreme human pressure should be designated as most important for in situ conservation approach.
Laboratory-based surveillance of non-tuberculous mycobacterial pulmonary disease in Japan
Authors: Hamaguchi Yuko , Morimoto Kozo , Mitarai Satoshi
Published: April 2024

Background

Intractable pulmonary diseases with non-tuberculous mycobacteria (NTM-PDs) and antimicrobial resistance have become increasingly concerning worldwide. Nevertheless, a surveillance system for NTM has not been established in most countries, thus requiring repeated, intermittent, and time-consuming cross-sectional nationwide surveys.

Methods

To establish a nationwide surveillance system for NTM-associated diseases, we aimed to develop a prototype computer system primarily designed to continuously estimate NTM-PD incidence using a bacteriological case-defining algorithm through an automatic process of integrating bacteriological data collected from microbiology laboratories across Japan. To validate the accuracy of our study results, we compared the distribution of pulmonary TB cases between our laboratory data and the national surveillance data, which is representative of the Japanese population.

Results

Our estimates implied a 17.7% increase in NTM-PD incidence from 15.8 [14.9–16.8] in 2013 to 19.2 [18.2–20.4] in 2017, per 100,000 population. Moreover, 93.0% of the identified NTM-PD cases were dominated by theMycobacterium avium-intracellularecomplex, and the proportion ofM. abscessusspecies exceeded that ofM. kansasiifor the first time in Japan. We also revealed significant age and sex differences in NTM-PDs. Notably, we found similar characteristics between our laboratory data and national surveillance data covering almost the entire Japanese population.

Conclusion

These findings, despite being laboratory-based, are extrapolatable to the general population in Japan and provide evidence that supports our system as a viable alternative to the nationwide NTM surveillance system.
Endovascular thrombectomy for acute ischemic stroke with a large infarct area: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Ravipati Shivani , Amjad Ayesha , Zulfiqar Komal , Biju Hannah , Hassan Wajeeh , Jafri Haider Mumtaz , Husnain Ali , Tahir Ibrahim , Aslam Muaaz , Afzal Sharib , Ehsan Muhammad , Cheema Huzaifa Ahmad , Ayyan Muhammad , Rehman Wajeeh Ur , Dani Sourbha S.
Published: April 2024

Background

Since the efficacy and safety of endovascular thrombectomy (EVT) in patients with acute ischemic stroke with a large infarct area is still inconclusive, we sought to compare functional and neurological outcomes with the use of endovascular thrombectomy versus medical care alone.

Methods

We searched MEDLINE (via PubMed), Embase, Cochrane Library, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) to retrieve all the relevant randomized controlled trials (RCTs) on this topic. Review manager (RevMan) was used to perform meta-analyses using a random-effect model. Dichotomous outcomes were pooled using risk ratios (RR) with 95% confidence intervals (CIs).

Results

Our meta-analysis included 6 RCTs with a total of 1665 patients. Most studies included patients with an ASPECTS score of 3-5. Our results demonstrate that endovascular thrombectomy significantly increased the rates of functional independence (mRS ≤ 2) (RR, 2.49; 95% CI, 1.89-3.29) and moderate neurological outcome (mRS ≤ 3) (RR, 1.90; 95% CI, 1.50-2.40) at 90 days. The benefit of EVT for these outcomes remained the same at 1-year follow-up.. Endovascular thrombectomy was associated with increased rates of early neurological improvement (RR, 2.22; 95% CI, 1.53-3.22), excellent neurological recovery (mRS ≤ 1) (RR, 1.75; 95% CI, 1.02-3.03), and decreased rate of poor neurological recovery (mRS 4-6) (RR, 0.81; 95% CI, 0.76-0.86). No significant difference was found between the two groups regarding all-cause mortality (RR, 0.86; 95% CI, 0.72-1.02), decompressive craniectomy (RR, 1.32; 95% CI, 0.89-1.94), and the incidence of serious adverse effects (RR, 1.39; 95% CI, 0.83-2.32) between the two groups. Endovascular thrombectomy significantly increased the rates of any intracranial hemorrhage (RR, 1.94; 95% CI, 1.48-2.53) and symptomatic intracranial hemorrhage (RR, 1.73; 95% CI, 1.11-2.69).

Conclusion

Endovascular thrombectomy (EVT) significantly improves neurological and functional outcomes in patients with acute ischemic stroke with a large infarct area (ASPECTS 3-5) compared to medical therapy alone, with an increased risk of symptomatic intracranial hemorrhage.
Evaluating self-triage accuracy of laypeople, symptom-assessment apps, and large language models: A framework for case vignette development using a representative design approach (RepVig)
Authors: Kopka Marvin , Napierala Hendrik , Privoznik Martin , Sapunova Desislava , Zhang Sizhuo , Feufel Markus A.
Published: April 2024

Most studies evaluating symptom-assessment applications (SAAs) rely on a common set of case vignettes that are authored by clinicians and devoid of context, which may be representative of clinical settings but not of situations where patients use SAAs. Assuming the use case of self-triage, we used representative design principles to sample case vignettes from online platforms where patients describe their symptoms to obtain professional advice and compared triage performance of laypeople, SAAs, and Large Language Models (LLMs) on representative versus standard vignettes. We found performance differences in all three groups depending on vignette type (OR = 1.27 to 3.41, p < .001 to .035) and changed rankings of best-performing SAAs and LLMs. Based on these results, we argue that our representative vignette sampling approach (that we call the RepVig Framework) should replace the practice of using a fixed vignette set as standard for SAA evaluation studies.
A simple mathematical model and physical device to estimate a woman-specific probability of skilled birth assistance and associated benefit of maternity waiting home stay
Authors: Gallien Jérémie , Chen George , Zhang Yi , Du Yuhang , Lori Jody , Sieka Joseph , Tehoungue Bentoe
Published: April 2024

This paper presents a simple mathematical model and an associated physical device to predict (i) the risk that a woman’s active labor will begin without a skilled birth attendant based on her parity and anticipated time to access skilled care; and (ii) the extent to which that risk may be reduced by moving to a maternity waiting home some time before her expected due date. This tool is designed to facilitate more systematic discussions and better-informed decisions about labour care access arrangements during antenatal consultations.