bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasonography as a Tool to Improve Preoperative Marking in Body Contour Surgery
Authors: Manzaneda Cipriani Raúl Martín , Viaro Maurício , Adrianzen Gerardo , Flores Emmanuel , Duran Vega Héctor , Babaitis Ricardo , Dal Ponte Zatt João Vitor , Salonia Goldmann Ignacio , Kornalewski de Oliveira Rafael , de Souza Bisognin Laura
Published: November 2023

Background:

Body contouring surgery and surgical drawings are usually performed based on the surgeon’s experience without considering the nature of the unique anatomical structures of each patient. Thus, we propose a more reliable surgical design approach that considers the anatomical structures of each patient. Ultrasonography is increasingly used in plastic surgery and helps plastic surgeons to highlight anatomical features representing results in their interventions by providing a better understanding of the patients’ unique structures.

Methods:

This study presents a series of cases involving 100 recruited patients (36 men and 64 women) between 18 and 60 years of age. Five surgeons examined the patients and created a presurgical design based on palpation, which was validated later by a physician skilled in evaluating the anterior wall of the abdomen using ultrasonography. The concordance between the findings of the palpation and ultrasonography was assessed for each patient.

Results:

The concordance rate for each structure in both evaluations was midline (49%) (P > 0.92), diastasis recti (15%), semilunar line (23%), upper edge of rectus abdominis muscles (12%), lower edge of pectoral muscles (16%), border of oblique muscle (13%), number of tendinous intersections (12%), shape of tendinous intersections (11%), serratus anterior muscle (15%), subcostal triangle (15%), and oblique triangle (26%) (P < 0.0001).

Conclusion:

All the structures evaluated by palpation in comparison with ultrasound show discordance, except the midline where agreement is evident, with a very good level of statistical significance.
Impact of an Institutional Clinical Pathway on Emergency Physicians’ Stated Preferences in Treating Patients with Low-Risk Pulmonary Embolism
Authors: Akhavan Arvin Radfar , O’Brien-Lambert Alex , Postiglione Nick , Schleyer Anneliese M. , Vrablik Marie , Hall M. Kennedy
Published: November 2023

Background:

Evidence continues to accumulate that select patients with acute low-risk pulmonary embolism (PE) can be safely discharged from the emergency department. Despite this, outpatient management continues to be uncommon. We report changes in emergency providers’ stated preferences on low-risk acute PE management before and after the development and implementation of an institutional clinical pathway and decision tool.

Methods:

We performed an observational analysis of attending emergency physicians’ stated preferences towards the management of low-risk acute PE using survey results before and after the development and implementation of an electronic health record-embedded institutional low-risk acute PE pathway.

Results:

Attending emergency medicine providers reported feeling more comfortable using PE risk stratification scores to identify dischargeable low-risk PE patients and also reported that they would be more likely to discharge a hypothetical patient with low-risk acute PE.

Conclusion:

Our results suggest that the implementation of an institutional clinical pathway with integration into the electronic health record was associated with a change in emergency physicians’ stated preferences for managing patients with acute low-risk PE in the emergency department. Implementation of an evidence-based standard pathway was associated with increased comfort and familiarity with PE risk stratification, and an increased comfort with and preference for early outpatient management of low-risk PE.
Long-term quality of life between duodenum-preserving pancreatic head resection and pancreatoduodenectomy: a systematic review and meta-analysis
Authors: Yin Taoyuan , Wen Jingjing , Zhen Tingting , Liao Yangwei , Zhang Zhenxiong , Zhu Hongtao , Wang Min , Pan Shutao , Guo Xingjun , Zhang Hang , Qin Renyi
Published: November 2023

Background:

We aimed to compare the differences in quality of life (QOL) and overall survival (OS) between DPPHR and PD during long-term follow-up. Duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD) have been shown to be effective in alleviating symptoms and controlling malignancies, but there is ongoing debate over whether DPPHR has an advantage over PD in terms of long-term benefits.

Method:

We searched the PubMed, Cochrane, Embase, and Web of Science databases for relevant studies comparing DPPHR and PD published before 1 May 2023. This study was registered with PROSPERO. Randomised controlled trials and non-randomised studies were included. The Mantel–Haenszel model and inverse variance method were used as statistical approaches for data synthesis. Subgroup analyses were conducted to evaluate the heterogeneity of the results. The primary outcome was the global QOL score, measured using the QLQ-C30 system.

Results:

We analysed ten studies involving 976 patients (456 DPPHR and 520 PD). The global QOL score did not differ significantly between the DPPHR and PD groups (standard mean difference [SMD] 0.21, 95% confidence interval [CI] [−0.05, 0.46], P=0.109, I

2
=70%); however, the OS time of patients with DPPHR was significantly improved (HR 0.59, 95% CI [0.44, 0.77], P<0.001, I

2
=0%). The follow-up length may be an important source of heterogeneity. Studies with follow-up length between two to seven years showed better global QOL for DPPHR than for PD (SMD 0.43, 95% CI [0.23, 0.64], P<0.001, I

2
=0%). There were no significant differences between the two groups in any of the functional scales of the QLQ-C30 system (all P>0.05). On the symptom scale, patients in the DPPHR group had lower scores for fatigue, nausea and vomiting, loss of appetite, insomnia, and diarrhoea than those in the PD group (all P<0.05).

Conclusion:

There were no significant differences in global QOL scores between the two surgeries; however, DPPHR had advantages over PD in terms of safer perioperative outcomes, lower long-term symptom scores, and longer OS times. Therefore, DPPHR should be recommended over PD for the treatment of benign pancreatic diseases and low-grade malignant tumours.
Breast density reduction as a predictor for prognosis in premenopausal women with estrogen receptor-positive breast cancer: an exploratory analysis of the updated ASTRRA study
Authors: Bae Soong June , Kim Hee Jeong , Kim Hyun-Ah , Ryu Jai Min , Park Seho , Lee Eun-Gyeong , Im Seock-Ah , Jung Yongsik , Park Min Ho , Park Kyong Hwa , Kang Su Hwan , Park Eunhwa , Kim Sung Yong , Lee Min Hyuk , Kim Lee Su , Lee Anbok , Noh Woo Chul , Gwark Sungchan , Kim Seonok , Jeong Joon
Published: November 2023

Background:

While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to anti-hormone therapy. We investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial.

Materials and Methods:

The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor (ER)-positive breast cancer after chemotherapy. We updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference.

Results:

We evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups (TAM-only group (106/476 [22.3%]) vs. TAM+OFS group (89/468 [19.0%]); P=0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM+OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR:0.37; 95% CI:0.16-0.85; P=0.019), but not in the TAM-only group (P
interaction=0.039). MDR-positive patients who received TAM+OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR:0.30; 95% CI:0.13-0.70; P=0.005).

Conclusion:

Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+OFS group.
Longitudinal changes in renal parenchymal volume and function status after partial nephrectomy: A retrospective cohort study
Authors: Xiong Longbin , Zou Xiangpeng , Luo Xin , Yin Shaohan , Huang Yixin , Ning Kang , Wen Dongxiang , Zhou Zhaohui , Wang Jun , Li Zhen , Chen Jiawei , Li Jibin , Peng Wei , Guo Shengjie , Dong Pei , Zhou Fangjian , Han Hui , Peng Yulu , Yu Chunping , Zhang Zhiling
Published: November 2023

Background:

The ipsilateral renal parenchymal volume (RPV) experiences a sharp decrease shortly after partial nephrectomy (PN), mainly due to surgical remove or devascularization of kidney tissue. However, the subsequent change of RPV and its association with GFR fast decline remains unknown. Our objective was to investigate the change of ipsilateral RPV and renal function status from new baseline (1-12 months after PN) to latest follow-up (≥1 year) after PN, and to explore factors associated with ipsilateral RPV decrease rate and correlation between RPV decrease and GFR fast decline.

Materials and Methods:

A retrospective review of 367 patients with PN was conducted. Three-dimensional reconstruction of CT/MRI images was performed for RPV calculation. Spectrum score was used to assess the degree of acute kidney injury (AKI) in the operated kidney after PN. GFR decline >3 ml/min/1.73 m2/year was defined as GFR fast decline. 114 patients underwent abdominal surgery was used as control. Predictive factors for subsequent decrease of RPV rate and GFR fast decline were evaluated by linear and logistic regression, respectively.

Results:

With a median interval time of 21.1 (IQR:13.8-35.5) months, median ipsilateral RPV significantly decreased from 118.7 (IQR:100.7-137.1) ml at new baseline to 111.8 (IQR:92.3-131.3) ml at latest follow-up. The interval time (β: 1.36 [0.71-2.01], P<0.001) and spectrum score (β: 5.83 [2.92-8.74], P<0.001) were identified as independent predictors of ipsilateral RPV decrease rate. GFR fast decline was observed in 101(27.5%) patients. Annual ipsilateral RPV decrease rate [OR:1.67(1.05–2.67), P=0.03] and overweight [OR:1.63(1.02–2.60), P=0.04] were independent predictors of GFR fast decline.

Conclusions:

Ipsilateral RPV experienced a moderate but significant decrease during follow-up after PN, especially in those with severer acute kidney injury. The presence of GFR fast decline was found to be associated with reduction of ipsilateral RPV, particularly in overweight individuals.
Amino acids and cancer: potential for therapies?
Authors: Siqueira Jéssika M. , Vega Maria C.M. Dela , Pimentel Gustavo D.
Published: November 2023

Purpose of review

Cancer patients may have a variety of disorders associated with systemic inflammation caused by disease progression. Consequently, we have protein hypercatabolism. In view of this, protein and amino acid adequacy should be considered in relation to nutritional behavior. Therefore, this review aims to evaluate the influence of protein and amino acids in the nutritional therapy of cancer.

Recent findings

Diets with adequate protein levels appear to be beneficial in the treatment of cancer; guidelines suggest consumption of greater than 1.0–1.5 g/kg body weight/day. In patients diagnosed with malnutrition, sarcopenia, or cachexia, it is recommended to use the maximum amount of protein (1.5 g/kg of weight/day) to adapt the diet. In addition, based on the evidence found, there is no consensus on the dose and effects in cancer patients of amino acids such as branched-chain amino acids, glutamine, arginine, and creatine.

When evaluating the components of the diet of cancer patients, the protein recommendation should be greater than 1.0–1.5 g/kg of weight/day, with a distribution between animal and vegetable proteins. We found little evidence demonstrating clinical benefits regarding individual or combined amino acid supplementation. Still, it is unclear how the use, dose, and specificity for different types of cancer should be prescribed or at what stage of treatment amino acids should be prescribed.
Bone mass accrual in children
Authors: Rodrick Eugene , Kindler Joseph M.
Published: November 2023

Purpose of review

Bone accrual during childhood and adolescence is critical for the attainment of peak bone mass and is a major contributing factor towards osteoporosis in later life. Bone mass accrual is influenced by nonmodifiable factors, such as genetics, sex, race, ethnicity, and puberty, as well as modifiable factors, such as physical activity and diet. Recent progress in bone imaging has allowed clinicians and researchers to better measure the morphology, density, and strength of the growing skeleton, thereby encompassing key characteristics of peak bone strength. In this review, the patterning of bone accrual and contributors to these changes will be described, as well as new techniques assessing bone mass and strength in pediatric research and clinical settings.

Recent findings

This review discusses factors influencing peak bone mass attainment and techniques used to assess the human skeleton.

The rate of bone accrual and the magnitude of peak bone mass attainment occurs in specific patterns varying by sex, race, ethnicity, longitudinal growth, and body composition. Physical activity, diet, and nutritional status impact these processes. There is a need for longitudinal studies utilizing novel imaging modalities to unveil factors involved in the attainment and maintenance of peak bone strength.
Pulmonology for the rhinologist
Authors: Campbell Raewyn G. , Auyeung Titus , Katsoulotos Gregory P.
Published: November 2023

Purpose of review

The upper and lower airways are inter-related despite serving different functions and can no longer be considered separately. Rhinologists are becoming increasingly aware of the role the lower airway plays in optimizing outcomes for their patients. This review highlights recent developments in pulmonology that impact rhinologic conditions.

Recent findings

The unified airway concept now supports the multidisciplinary management of respiratory and rhinologic pathologies. Biomarkers, biologics and the concept of treatable traits have permitted the development of personalized and precise treatment of the entire respiratory tract. The concept of corticosteroid stewardship, the introduction of steroid sparing agents for the treatment of respiratory diseases and the development of biomarkers, now forces us to be more considerate and precise with oral corticosteroid (OCS) prescribing and to consider reduction regimens. Finally, current research on climate change and vaping will allow us to better educate and prepare our patients to improve adherence and avoid exacerbations to maintain optimal global respiratory health.

The inter-relatedness of the upper and lower airway has encouraged a multidisciplinary focus in respiratory medicine. More research is required to improve the precision respiratory medicine model, particularly in the realm of biomarkers and endotyping. These developments must also consider the impact of climate change, pollution and toxins for us to provide optimum care for our patients.
Infectious disease for the rhinologist
Authors: Png Lu Hui , Ng Dorothy Hui Lin , Teo Neville Wei Yang
Published: November 2023

Purpose of review

The purpose of this review is to summarize the recent literature relating to viral, fungal and bacterial infections and their interactions within the sinonasal tract in the past 18 months.

Recent findings

Coronavirus disease 2019 (COVID-19)-associated olfactory dysfunction (OD) is variant dependent. Magnetic resonance imaging studies have found greater olfactory cleft opacification and higher olfactory bulb volume in post-COVID-19 OD. Olfactory training remains the mainstay of treatment, while platelet-rich plasma injections and ultramicronized palmitoylethanolamide and luteolin combination oral supplementation have shown early promise.

Consensus statements on paranasal sinus fungal balls and acute invasive fungal sinusitis have been released.

Studies on the nasal microbiome have reported Staphylococcus and Corynebacterium as the most abundant genera, with higher levels of Staphylococcus and Corynebacterium being found in patients with chronic rhinosinusitis (CRS) and healthy individuals respectively. However, there is conflicting evidence on the significance of biodiversity of the nasal microbiome found in CRS versus healthy patients.

While the peak of the COVID-19 pandemic is behind us, its sequelae continue to pose treatment challenges. Further studies in OD have implications in managing the condition, beyond those afflicted post-COVID-19 infection. Similarly, more research is needed in studying the nasal microbiome and its implications in the development and treatment of CRS.
Management of hyperkalemia in children
Authors: Janjua Halima
Published: November 2023

Purpose of review

Hyperkalemia is a potentially fatal electrolyte abnormality with no standardized management. The purpose of this review is to provide the knowledge needed for timely and effective management of hyperkalemia in children. It describes the utility of existing and novel therapies.

Recent findings

Two newer oral potassium binding agents, patiromer sorbitex calcium and sodium zirconium cyclosilicate, have been FDA-approved for the management of hyperkalemia in adults. These newer agents offer hope for improved management, even though their use in pediatric patients requires further exploration.

This review highlights the causes and life-threatening effects of hyperkalemia and provides a comprehensive overview of the management of hyperkalemia in both acute and chronic settings along with upcoming treatment strategies.
Magnitude of dural tear and its associated factors among patients with depressed skull fracture
Authors: Molla Yohannis D. , Alemu Hirut T. , Kassa Samrawit A. , Gebrehana Deresse A. , Abera Samuel A. , Tebeje Helina E. , Demise Abel G.
Published: November 2023

Introduction:

Trauma is a huge problem seen in developed countries as well as developing countries. Head injury is a major factor responsible for mortality in young populations. Up to 6% of all head injuries and 11% of severe head traumas might result in a depressed skull fracture (DSF), a catastrophic injury. The aim of this study was to determine the prevalence of dural tear and to identify its predictors.

Method:

A retrospective review of medical records of all patients operated on for DSFs at the University Comprehensive Specialized Hospital from 1 January 2021 to 1 January 2023 G.C. (Gregorian calendar) was conducted. A total of 163 patients were included in the study.

Results:

A total of 163 patients [136 men (83.4%) and 27 women (16.6%)] had a mean age of 23.9 with a standard deviation of 14.8 (range from 3 to 65). Patients with penetrating injuries (missiles, axes) were excluded. The majority, 153 (93.9%) of the patients, were younger than 50 years of age. Physical assault accounted for 102 (62.5%) of the cases. Of the assaulted cases, 62 (38%) were assaulted by stone, 32 (19.6%) by stick, and 8 (5%) by other objects (beer bottle and shovel). Bleeding from the trauma site in 124 (76.1%), headache in 76 (46.6%), loss of consciousness in 75 (46%), and vomiting in 72 (44.2%) were the most common presentations. Based on the Glasgow Coma Scale (GCS), 123 (75%) patients had mild head injuries. Based on the site of fracture, frontal depressions are the most common (61, 37.4%), followed by parietal depressions (53, 32.5%). With regard to the associated injuries, brain contusion was seen in 52 (32%), epidural hematoma (EDH) in 26 (16%), subdural hematoma in 3 (1.8%), and intraventricular hemorrhage/subarachnoid hemorrhage (IVH/SAH) in 3 (1.8%). The median duration of presentation was 15 h, with an interquartile range (IQR) of 8–24 (1–96 h). From the multivariable logistic regression, brain contusion and EDH were significantly associated with dural tear.

Conclusion:

The rules of our culture are reflected in the higher incidence of accidents and fractures among men. Physical assault, particularly with stones, was the most common cause of DSFs. Frontal depressions were the most common site of fracture, followed by parietal fractures. Brain contusion and EDH were significantly associated with dural tears. School-aged children are more vulnerable to injuries from horse or donkey kicks and falls.
Does Prophylactic Closure Improve Outcomes After Colorectal Endoscopic Submucosal Dissection? A Systematic Review and Meta-analysis
Authors: Dong Liang , Zhu Weihua , Zhang Xiaolei , Xie Xiao
Published: November 2023

Background:

Several studies have described prophylactic closure after endoscopic submucosal dissection (ESD) of colorectal lesions for improving postoperative outcomes. We reviewed the evidence on the impact of prophylactic closure after ESD.

Methods:

A literature search was conducted on PubMed, Embase, CENTRAL, and Web of Science by 2 reviewers independently for studies published up to July 9, 2023. All types of comparative studies were eligible.

Results:

Ten studies compared 939 patients undergoing prophylactic closure with 1074 controls. Three were randomized controlled trials (RCTs) while the rest were observational. Pooled data from all included studies showed that prophylactic closure resulted in reduced incidence of delayed bleeding after ESD [odds ratio (OR): 0.30; 95% CI: 0.15, 0.72; I
2=0%]. These results were significant only for observational studies but not for RCTs. Meta-analysis showed no significant difference in the risk of delayed perforation (OR: 0.55; 95% CI: 0.18, 1.70; I
2=0%) or post-ESD coagulation syndrome (PECS) (OR: 1.15; 95% CI: 0.41, 3.19; I
2=63%) between closure and nonclosure groups.

Conclusions:

Observational data suggest that prophylactic closure of colorectal mucosal defects after ESD may reduce the risk of delayed bleeding. However, the results are not concurred by RCTs. Furthermore, there seems to be no impact of prophylactic closure on the risk of delayed perforation and PECS.
Well-being biomarkers and psychological functioning of adult patients during chemotherapy treatment: the effects of hospital clowns and hosting conditions
Authors: Simões Marta , Oliveira Albertina , Pinheiro Rosário , Vilar Manuela , Agante Diana , Pazos Isabel , Oliveiros Bárbara , Grazina Manuela
Published: November 2023

Background

Pharmacological oncological treatments interfere with the patient’s quality of life on physical, psychological, and social dimensions. Besides all the care in hosting conditions, hospital clowns (HCs) use artistic sketches aiming to reduce distress, but studies analyzing their effects on biomarkers in association with psychological states are scarce. This study examined biomarkers and psychological functioning related to its effects, in adult patients of an ambulatory chemotherapy hospital setting.

Methods

Following a pilot study with pre-testing/post-testing, 64 women were analysed: experimental group (EG; n=36; HCs intervention plus hosting conditions)versuscontrol group (CG; n=28; hosting conditions). Oxytocin, cortisol, serotonin and ATP saliva levels were measured. Psychological assessment covered positive and negative affect (PA; NA), emotional states (PESS), mindfulness attention’ quality (CAMS-R), cognitive functioning (CDT) and satisfaction with HCs.

Results

Data did not reveal statistically significant differences in biomarkers between groups; EG showed improvements in psychological functioning, in which NA had significantly decreased, compared to CG; PESS and CAMS-R have also improved. Association analyses suggest a role of serotonin in moderating the relationship between (PA&scholarity)&CAMS-R with NA&age; serotonin and ATP changes are more related to psychological features; PESS seems to modulate those relationships in EG.

Conclusions

Although similar results were found for the two groups in study, concerning biomarkers, the psychological functioning showed that short-term interventions during ambulatory chemotherapy might increase well-being of adult cancer patients. Certainly, a larger sample is needed, both to ascertain salivary biomarkers variations and psychological benefits, but this study is undoubtedly pioneer.
Gaining Biological Insights through Supervised Data Visualization
Authors: Rhodes Jake S. , Aumon Adrien , Morin Sacha , Girard Marc , Larochelle Catherine , Brunet-Ratnasingham Elsa , Pagliuzza Amélie , Marchitto Lorie , Zhang Wei , Cutler Adele , Grand’Maison Francois , Zhou Anhong , Finzi Andrés , Chomont Nicolas , Kaufmann Daniel E. , Zandee Stephanie , Prat Alexandre , Wolf Guy , Moon Kevin R.
Published: November 2023

Dimensionality reduction-based data visualization is pivotal in comprehending complex biological data. The most common methods, such as PHATE, t-SNE, and UMAP, are unsupervised and therefore reflect the dominant structure in the data, which may be independent of expert-provided labels. Here we introduce a supervised data visualization method called RF-PHATE, which integrates expert knowledge for further exploration of the data. RF-PHATE leverages random forests to capture intricate featurelabel relationships. Extracting information from the forest, RF-PHATE generates low-dimensional visualizations that highlight relevant data relationships while disregarding extraneous features. This approach scales to large datasets and applies to classification and regression. We illustrate RF-PHATE’s prowess through three case studies. In a multiple sclerosis study using longitudinal clinical and imaging data, RF-PHATE unveils a sub-group of patients with non-benign relapsingremitting Multiple Sclerosis, demonstrating its aptitude for time-series data. In the context of Raman spectral data, RF-PHATE effectively showcases the impact of antioxidants on diesel exhaust-exposed lung cells, highlighting its proficiency in noisy environments. Furthermore, RF-PHATE aligns established geometric structures with COVID-19 patient outcomes, enriching interpretability in a hierarchical manner. RF-PHATE bridges expert insights and visualizations, promising knowledge generation. Its adaptability, scalability, and noise tolerance underscore its potential for widespread adoption.
scSniper: Single-cell Deep Neural Network-based Identification of Prominent Biomarkers
Authors: Li Mingyang , Chen Yanshuo , Ding Jun
Published: November 2023

Discovering disease biomarkers at the single-cell level is crucial for advancing our understanding of diseases and improving diagnostic accuracy. However, current computational methods often have limitations, such as a reliance on prior knowledge, constraints to unimodal data, and the use of conventional statistical tests for feature selection. To address these issues, we introduce scSniper, a novel approach that employs a specialized deep neural network framework tailored for robust single-cell multiomic biomarker detection. A standout feature of scSniper is the mimetic attention block, enhancing alignment across multi-modal data types. Moreover, scSniper utilizes sensitivity analysis based on a deep neural network for feature selection and uncovers intricate gene regulatory networks without requiring prior knowledge. Comprehensive evaluations on real-world datasets, including COVID-19 CITE-Seq and LUAD scRNA-Seq, demonstrate scSniper’s exceptional ability to identify critical biomarkers consistently outperforming traditional methods like MAST, Wilcox, and DESeq2. The scSniper tool and related experimental codes are publicly accessible athttps://github.com/mcgilldinglab/scSniper.
Assessment of a bronchodilator response in preschoolers: a systematic review
Authors: Wong Matthew D. , Condon Kathleena , Robinson Paul D. , Suresh Sadasivam , Zahir Syeda Farah , Sly Peter D. , Blake Tamara L.
Published: November 2023

Background

A bronchodilator response (BDR) can be assessed in preschool-aged children using spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance, yet a systematic comparison of BDR thresholds across studies has not been completed.

Methods

A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts.

Results

Of 1224 screened studies, 43 were included. Over 85% were from predominantly Caucasian populations, and only 22 studies (51.2%) calculated a BDR cut-off based on a healthy control group. Sample sizes ranged from 25-916. Only two studies (4.6%) adhered to formal recommendations for study design: at least 300 subjects, randomised for placebo response testing in healthy children, and incorporated within-session and between-session test repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. A variety of statistical methods were used to define a BDR. The highest BDR feasibility was reported with oscillometry techniques in this age group.

Conclusion

A BDR in 2-6-year-olds cannot be defined based on the reviewed literature due to inconsistent methodology and cut-off calculations. Precise and feasible evaluation of lung function in young children is crucial for early detection and intervention of airway diseases. A standardised approach is required to develop robust BDR thresholds.
Factors that lead to patient mistrust of the healthcare system in Hargeisa, Somaliland: a qualitative exploration
Authors: Ahmed Hersi Y , Mussa Abdillahi A , Yousuf Abdisamed M , Mohamed Hamda H , Ali Nimao A , Ahmed Zakhiya M , Abdi Yousuf M
Published: November 2023

Purpose

this research aimed to identify the factors that lead to patients having mistrust towards the healthcare system in Somaliland and use the findings as a foundation for future policies.

Methods

a descriptive study was conducted to understand the factors contributing to the population’s mistrust of the healthcare system in Hargeisa. Data was collected through interviews with 49 participants using a survey questionnaire administered by interviewers, and convenience sampling was used to select participants based on availability and accessibility.

Results

through our analysis, we identified 11 themes that investigate issues influencing healthcare quality, cost, and accessibility, such as financial barriers, diagnostic accuracy, drug use, equipment quality, laboratory role, doctor knowledge and skills, medical ethics, governance, local doctor reputation, foreign healthcare, and the quality of available healthcare services.

Conclusion

patient -physician mistrust in Somaliland can be addressed by implementing laws, examining doctors’ knowledge, and examining hospital facilities. Improving public health sectors and limiting patient payments can reduce healthcare costs. Regulations on drugs can reduce medication errors and restore trust in the healthcare system.
Detection and spread of high pathogenicity avian influenza virus H5N1 in the Antarctic Region
Authors: Bennison Ashley , Byrne Alexander M. P. , Reid Scott M. , Lynton-Jenkins Joshua G. , Mollett Benjamin , Silva Dilhani De , Peers-Dent Jacob , Finlayson Kim , Hall Rosamund , Blockley Freya , Blyth Marcia , Falchieri Marco , Fowler Zoe , Fitzcharles Elaine M. , Brown Ian H. , James Joe , Banyard Ashley C.
Published: November 2023

Until recent events, the Antarctic was the only major geographical region in which high pathogenicity avian influenza virus (HPAIV) had never previously been detected. The current panzootic of H5N1 HPAIV has decimated wild bird populations across Europe, North America, and South America. Here we report on the detection of clade 2.3.4.4b H5N1 HPAIV in the Antarctic and sub-Antarctic regions of South Georgia and the Falkland Islands, respectively. We initially detected H5N1 HPAIV in samples collected from brown skuas at Bird Island, South Georgia on 8thOctober 2023. Since this detection, mortalities were observed in brown skuas, kelp gulls, South Georgia shag, Antarctic tern, elephant seals and fur seals at multiple sites across South Georgia. Subsequent testing confirmed H5N1 HPAIV across several sampling locations in multiple avian species and two seal species. Simultaneously, we also confirmed H5N1 HPAIV in southern fulmar and black-browed albatross in the Falkland Islands. Genetic assessment of the virus indicates spread from South America, likely through movement of migratory birds. Critically, genetic assessment of sequences from mammalian species demonstrates no increased risk to human populations. Here we describe the detection, species impact and genetic composition of the virus and propose both introductory routes and potential long-term impact on avian and mammalian species across the Antarctic region. We also speculate on the threat to specific populations following recent reports in the area.
Loss of neuronatin increases susceptibility of SERCA to thermal inactivation
Authors: Barfoot Michael , Fajardo Val A. , Braun Jessica L.
Published: November 2023

Phospholamban and sarcolipin are two key regulators of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) that have been shown to protect SERCA from thermal inactivation in muscle

We have recently detected neuronatin (NNAT) in murine skeletal muscle and have shown that it too regulates SERCA

Here, we questioned whether NNAT would also protect SERCA from thermal inactivation

In response to 60 min of heat stress at 40°C, maximal SERCA activity was significantly reduced in soleus homogenates obtained from NNAT knockout mice (-23%) but not wild-type mice (-5%).

Our results add further support for NNAT’s role in regulating SERCA function in murine muscle
Unmasking Hidden Systemic Effects of Neurodegenerative Diseases: A Two-Pronged Approach to Biomarker Discovery
Authors: Anjo Sandra I. , Rosado Miguel , Baldeiras Inês , Gomes Andreia , Pires Diana , Santa Cátia , Pinto Joana , Januário Cristina , Santana Isabel , Verdelho Ana , de Mendonça Alexandre , Castelo-Branco Miguel , Manadas Bruno
Published: November 2023

Identification of reliable blood biomarkers for neurodegenerative diseases (NDs) is crucial for translational and clinical research. However, conventional omics struggle with blood samples complexity, hindering desired outcomes. In this work the potential of High Molecular Weight (HMW) fractionation under non-denaturing conditions as a complementary approach to the conventional proteomics for identifying serum biomarkers in NDs was explored. A cohort of 58 serum samples of Alzheimer’s disease (AD), Parkinson’s disease (PD) patients and control (CT) individuals was used to compare the two proteomics strategies: i) direct analysis of whole serum and ii) non-denaturing fractionation using 300 kDa cut-off filters (HMW serum).

Although both approaches quantified a similar set of proteins, each approach captured a distinct subset of differentially altered proteins, suggesting that HMW fractionation identified additional types of alterations beyond conventional protein level changes. A discriminant model combining altered proteins from both datasets effectively distinguished between the three groups (AUC = 0.999 and median sensitivity and specificity of 97.4% and 91.7%, respectively). Importantly, this performance surpassed that of any model created using each method individually.

Altogether, this work demonstrated that HMW fractionation can be a valuable complementary method to direct serum analysis and could enhance biomarker discovery. The 10 proteins included in the model (5 from each strategy), comprise clear evidence for the contribution of apolipoproteins for the diagnosis of NDs, revealing potential changes within lipid metabolism and the organization of macromolecules and their complexes, thereby uncovering effects that remain hidden from a conventional serum proteome analysis.
How do sapling and adult demography explain beech predominance along environmental gradients in Central European forests?
Authors: Heiland Lukas , Kunstler Georges , Hülsmann Lisa
Published: November 2023

Understanding how species abundances are driven by biotic interactions along environmental gradients is a fundamental question in ecology. For abundances at competitive equilibria in Central European forests, a classical ecological theory formulated by Ellenberg (1963) predicts that beech (Fagus sylvaticaL.) outcompetes other tree species within a mesic range of soil pH and water levels, while other species prevail under less favorable conditions. While the theory is generally accepted in forest ecology, only certain aspects of it have been substantiated by empirical evidence. Moreover, the demographic processes driving the turnover from beech to other tree species at the extremes of the soil gradients remain mostly unexplained.

To address this, we inversely calibrated a parsimonious forest model (JAB model) with a sapling stage and interacting populations with short time series of observed tree abundances from the German national forest inventory. By modelling how demographic rates vary along pH and soil water gradients, we were able to test the prediction that beech naturally predominates only at favorable soil conditions. Moreover, we tested with simulations how the environmental response of demographic rates explainsFagus’ changing relative abundance along the soil gradients.

Our results largely confirm thatFagusout competes other species in a central environmental range. Environmental change ofFagus’ relative abundance is primarily explained by environmental variation of its net basal area increment, followed by its competition response at the overstory and at the sapling stage. We found that even though sapling tolerance to shading is the primary mechanism forFaguspredominance, it only plays a secondary role for the environmental variation of its relative abundance.

Synthesis:By inverse calibration of a forest population model with demographic rates that respond to the environment, we confirm the predictions of Ellenberg’s classical, albeitonlypartially-evidenced, theory onF. sylvatica’s predominance in Central European forests. Furthermore, for thefirsttime, we substantiate the theory by elucidating how the environmental variation in species composition is based in demographic processes. This demonstrates that our approach can be utilized to predict distributions of interacting species and to explain the dynamics between species, as influenced by their environment.
Fluorescent human RPA to track assembly dynamics on DNA
Authors: Kaushik Vikas , Chadda Rahul , Kuppa Sahiti , Pokhrel Nilisha , Vayyeti Abhinav , Grady Scott , Arnatt Chris , Antony Edwin
Published: November 2023

DNA metabolic processes including replication, repair, recombination, and telomere maintenance occur on single-stranded DNA (ssDNA). In each of these complex processes, dozens of proteins function together on the ssDNA template. However, when double-stranded DNA is unwound, the transiently open ssDNA is protected and coated by the high affinity heterotrimeric ssDNA binding Replication Protein A (RPA). Almost all downstream DNA processes must first remodel/remove RPA or function alongside to access the ssDNA occluded under RPA. Formation of RPA-ssDNA complexes trigger the DNA damage checkpoint response and is a key step in activating most DNA repair and recombination pathways. Thus, in addition to protecting the exposed ssDNA, RPA functions as a gatekeeper to define functional specificity in DNA maintenance and genomic integrity. RPA achieves functional dexterity through a multi-domain architecture utilizing several DNA binding and protein-interaction domains connected by flexible linkers. This flexible and modular architecture enables RPA to adopt a myriad of configurations tailored for specific DNA metabolic roles. To experimentally capture the dynamics of the domains of RPA upon binding to ssDNA and interacting proteins we here describe the generation of active site-specific fluorescent versions of human RPA (RPA) using 4-azido-L-phenylalanine (4AZP) incorporation and click chemistry. This approach can also be applied to site-specific modifications of other multi-domain proteins. Fluorescence-enhancement through non-canonical amino acids (FEncAA) and Förster Resonance Energy Transfer (FRET) assays for measuring dynamics of RPA on DNA are also described.

Highlights

RPA is an essential protein for most DNA metabolic processes including replication, repair, and recombination.

RPA is a ssDNA binding protein made of six domains situated across RPA70, RPA32 and RPA14 subunits. Four high affinity DNA binding domains engage the DNA.

Site-specific fluorescent probes were incorporated into two domains of RPA and report on ssDNA binding dynamics.

Bulk-level kinetic and single-molecule assays are described to monitor the binding and remodeling of individual RPA domains on ssDNA.
The regulatory landscape of 5′ UTRs in translational control during zebrafish embryogenesis
Authors: Reimão-Pinto Madalena M. , Castillo-Hair Sebastian M. , Seelig Georg , Schier Alex F.
Published: November 2023

The 5′ UTRs of mRNAs are critical for translation regulation, but theirin vivoregulatory features are poorly characterized. Here, we report the regulatory landscape of 5′ UTRs during early zebrafish embryogenesis using a massively parallel reporter assay of 18,154 sequences coupled to polysome profiling. We found that the 5′ UTR is sufficient to confer temporal dynamics to translation initiation, and identified 86 motifs enriched in 5′ UTRs with distinct ribosome recruitment capabilities. A quantitative deep learning model, DaniO5P, revealed a combined role for 5′ UTR length, translation initiation site context, upstream AUGs and sequence motifs onin vivoribosome recruitment. DaniO5P predicts the activities of 5′ UTR isoforms and indicates that modulating 5′ UTR length and motif grammar contributes to translation initiation dynamics. This study provides a first quantitative model of 5′ UTR-based translation regulation in early vertebrate development and lays the foundation for identifying the underlying molecular effectors.

Highlights

In vivoMPRA systematically interrogates the regulatory potential of endogenous 5′ UTRs

The 5′ UTR alone is sufficient to regulate the dynamics of ribosome recruitment during early embryogenesis

The MPRA identifies 5′ UTRcis-regulatory motifs for translation initiation control

5′ UTR length, upstream AUGs and motif grammar contribute to the differential regulatory capability of 5′ UTR switching isoforms
Male boldness and female parental care predict reproductive success in a bi-parental cichlid, the rainbow krib (Pelvicachromis pulcher)
Authors: Scherer U. , Niemelä P.T. , Schuett W.
Published: November 2023

Animal personality differences, i.e. consistent among-individual behavioural differences within populations, are prevalent across the animal kingdom. However, we are just beginning to understand the adaptive significance of the observed behavioural variation. We are particularly in need of empirical studies testing hypotheses of proposed theoretical frameworks aiming to understand the existence animal personality differences. In this study, we investigated a hypothesis derived from a framework suggesting that sexual selection may generate and maintain personality variation. The authors of this framework propose parental care as a mechanism linking animal personality and reproductive fitness.

We repeatedly measured individual boldness in male and female rainbow kribs,Pelvicachromis pulcher, a West African cichlid known for territorial cave breeding and shared parental care. We then formed 54 breeding pairs with varying behavioural contrasts in boldness. For pairs that produced offspring (N = 20), we repeatedly recorded parental care behaviour (parental boldness and brood guarding) of both parents over one month. Reproductive success was measured as the likelihood to reproduce, the number of offspring, and offspring size at the end of breeding.

In both sexes, we found consistent among-individual differences in boldness before breeding and in parental care behaviours. Bolder males were less likely to reproduce but, when breeding was successful, produced bigger broods compared to less bold males. Female parental boldness positively correlated with the number of offspring produced. However, individual boldness before breeding did not predict parental care behaviour in either sex and we found no effects of the pairs’ contrast in prebreeding boldness on parental care coordination or reproductive success.

The outcomes of our study may suggest that among-individual variation in male boldness is maintained by males with different behavioural types playing different reproductive strategies of equal average fitness. Future research should delve into understanding the intricate link between male boldness and reproductive success, exploring for instance underlying genetic mechanisms and interactions with environmental conditions.
DAR1 - An Easy to Use, Single-Box, Configuration of a Global Scale Biogeochemical Ecosystem Model
Authors: Duckworth Barbara , Dutkiewicz Stephanie , Jahn Oliver , Hill Christopher N. , Follett Christopher L.
Published: November 2023

Global scale biogeochemical ocean models are key to understanding the mechanisms which drive elemental cycles and their links to marine ecosystems. However, these models are rarely straightforward to use and their complexity can make them difficult to interpret. Here, we aim to address this problem by developing DAR1 – a single box configuration of the MIT Darwin model, which is itself a global scale biogeochemical ecosystem model designed for understanding the emergent patterns of global plankton distributions. Our configuration is packaged inside Docker and implemented in the Julia programming language. This helps make it both computationally efficient and straightforward to implement on any local machine, independent of hardware and operating system. It allows for the replication of field and laboratory experiments in a model ocean and the rapid comparison of global runs with local predictions. We provide three case studies: a framework for nutrient amendment bottle experiments; a test of steady state assumptions on plankton community structure at the global scale; and an exploration of the niche space of nitrogen-fixing plankton. Our method has the potential to facilitate broader direct testing of global model assumptions in the context of small-scale measurements. DAR1 will also allow observational and laboratory oceanographers to directly test their results against model predictions in a straightforward, easy to use, manner.