bluuebunny/crossref_metadata_2025 huggingface dataset:
ETLD: an encoder-transformation layer-decoder architecture for protein contact and mutation effects prediction
Authors: Wang He , Zang Yongjian , Kang Ying , Zhang Jianwen , Zhang Lei , Zhang Shengli
Published: August 2023

The latent features extracted from the multiple sequence alignments (MSAs) of homologous protein families are useful for identifying residue–residue contacts, predicting mutation effects, shaping protein evolution, etc. Over the past three decades, a growing body of supervised and unsupervised machine learning methods have been applied to this field, yielding fruitful results. Here, we propose a novel self-supervised model, called encoder-transformation layer-decoder (ETLD) architecture, capable of capturing protein sequence latent features directly from MSAs. Compared to the typical autoencoder model, ETLD introduces a transformation layer with the ability to learn inter-site couplings, which can be used to parse out the two-dimensional residue–residue contacts map after a simple mathematical derivation or an additional supervised neural network. ETLD retains the process of encoding and decoding sequences, and the predicted probabilities of amino acids at each site can be further used to construct the mutation landscapes for mutation effects prediction, outperforming advanced models such as GEMME, DeepSequence and EVmutation in general. Overall, ETLD is a highly interpretable unsupervised model with great potential for improvement and can be further combined with supervised methods for more extensive and accurate predictions.
Differential variability analysis of single-cell gene expression data
Authors: Liu Jiayi , Kreimer Anat , Li Wei Vivian
Published: August 2023

The advent of single-cell RNA sequencing (scRNA-seq) technologies has enabled gene expression profiling at the single-cell resolution, thereby enabling the quantification and comparison of transcriptional variability among individual cells. Although alterations in transcriptional variability have been observed in various biological states, statistical methods for quantifying and testing differential variability between groups of cells are still lacking. To identify the best practices in differential variability analysis of single-cell gene expression data, we propose and compare 12 statistical pipelines using different combinations of methods for normalization, feature selection, dimensionality reduction and variability calculation. Using high-quality synthetic scRNA-seq datasets, we benchmarked the proposed pipelines and found that the most powerful and accurate pipeline performs simple library size normalization, retains all genes in analysis and uses denSNE-based distances to cluster medoids as the variability measure. By applying this pipeline to scRNA-seq datasets of COVID-19 and autism patients, we have identified cellular variability changes between patients with different severity status or between patients and healthy controls.
Self-supervised learning with chemistry-aware fragmentation for effective molecular property prediction
Authors: Xie Ailin , Zhang Ziqiao , Guan Jihong , Zhou Shuigeng
Published: August 2023

Molecular property prediction (MPP) is a crucial and fundamental task for AI-aided drug discovery (AIDD). Recent studies have shown great promise of applying self-supervised learning (SSL) to producing molecular representations to cope with the widely-concerned data scarcity problem in AIDD. As some specific substructures of molecules play important roles in determining molecular properties, molecular representations learned by deep learning models are expected to attach more importance to such substructures implicitly or explicitly to achieve better predictive performance. However, few SSL pre-trained models for MPP in the literature have ever focused on such substructures. To challenge this situation, this paper presents a Chemistry-Aware Fragmentation for Effective MPP (CAFE-MPP in short) under the self-supervised contrastive learning framework. First, a novel fragment-based molecular graph (FMG) is designed to represent the topological relationship between chemistry-aware substructures that constitute a molecule. Then, with well-designed hard negative pairs, a is pre-trained on fragment-level by contrastive learning to extract representations for the nodes in FMGs. Finally, a Graphormer model is leveraged to produce molecular representations for MPP based on the embeddings of fragments. Experiments on 11 benchmark datasets show that the proposed CAFE-MPP method achieves state-of-the-art performance on 7 of the 11 datasets and the second-best performance on 3 datasets, compared with six remarkable self-supervised methods. Further investigations also demonstrate that CAFE-MPP can learn to embed molecules into representations implicitly containing the information of fragments highly correlated to molecular properties, and can alleviate the over-smoothing problem of graph neural networks.
BJS 2 Pancreatoduodenectomy for malignancy: which patients are high-risk? Results from an international multicentre cohort study
Authors: Russell Thomas , Labib Peter , Aroori Somaiah ,   RAW Study Collaborators
Published: August 2023

Aims

Pancreatoduodenectomy (PD) is indicated in fit patients with a resectable cancer affecting the pancreatic head but morbidity rates remain high. This study aimed to identify risk factors for postoperative complications and perioperative mortality.

Methods

Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD patients with confirmed malignancy (29 centres, eight countries). Patients who experienced any complication, clinically relevant postoperative pancreatic fistula (CR-POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were compared to those who did not experience these outcomes.

Results

1348 patients were included. Any complication, major morbidity, CR-POPF, PPH and 90-day mortality affected 53.4%, 16.9%, 10.5%, 6.2% and 3.8% of patients, respectively. Following a multivariable analysis, high body mass index (BMI, OR: 1.1, p=0.007), American Society of Anesthesiologists (ASA) grade >II (OR: 2.2, p<0.0001) and a pylorus-resecting approach (OR: 1.6, p=0.005) correlated with overall morbidity. ASA >II patients were at increased risk of major morbidity (OR: 2.2, p<0.0001) and a raised BMI was a risk factor for CR-POPF (OR: 1.1, p=0.001). ASA >II (OR: 2.5, p=0.002) and positive lymph nodes on preoperative imaging (OR: 2.1, p=0.01) were risk factors for PPH, and both preoperative diabetes (OR: 0.4, p<0.05) and a pancreato-jejunostomy anastomosis (OR: 0.5, p=0.03) were protective. No risk factors for 90-day mortality were identified.

Conclusion

In our study, a high BMI and ASA grade >II were associated with adverse perioperative outcomes. Patients in these groups should be made aware of their increased risk prior to surgery.
SP2.4 The impact of preoperative American Society of Anesthesiologists grade on major pancreatoduodenectomy outcomes
Authors: Grayson Niamh , Ribaud Juliette , Mariathasan Michael , Nair Ashitha ,   RAW Study Collaborators, Srinivasan Parthi
Published: August 2023

American Society of Anesthesiologists (ASA) grade is often used as a crude assessment for grading patients prior to major surgery, such as pancreaticoduodenectomy (PD). Patients deemed to have a high ASA grade may not be offered resection. Increasing ASA grade is known to correlate with increasing morbidity and mortality rates. Prior authors have argued that caution should be used when offering PD to ASA grade >II patients. This study aimed to compare the outcomes of PD patients with a low ASA grade (I-II) with high ASA grade (>II).

Data was extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes following PD performed for pancreatic head malignancy (29 centres in 8 countries, n=1484). Patients were grouped by their ASA grade. The outcomes of interest were median length of stay (LoS), 30-day readmission, 90-day mortality and five-year survival. Comparisons were made using the Mann-Whitney U test and the Fisher exact test.

Out of 1484 cases, 1365 (92.0%) had information regarding their ASA grade available. Of these, 973 (71.3%) were ASA grade I-II and 392 (28.7%) were ASA grade >II. Whilst those with a high ASA grade had significantly longer LoS (14 vs 13 days, p<0.0001), 30-day readmission (8.5% vs 11.7% p=0.1), 90-day mortality (3.1% vs 4.6%, p=0.2) and five-year survival (32.5% vs 28.8%) rates were similar.

In our multicentre study of PD patients, high ASA grade correlated with increased LoS. However, a high ASA grade did not affect the other studied outcomes. Therefore, higher ASA grade alone should not be an absolute contraindication to PD.
ThTP1.9 The impact of patient gender on key outcomes of pancreatoduodenectomy: should gender influence patient selection?
Authors: Russell Thomas , Labib Peter ,   RAW Study Collaborators, Aroori Somaiah
Published: August 2023

Aims

Patients with a suspected cancer affecting the pancreatic head or periampullary region may be offered curative-intent pancreatoduodenectomy providing they are fit enough. Due to the high-risk nature of the operation and high recurrence rates, outcomes are poor. This study aimed to investigate the impact of patient gender on key short- and long-term outcomes.

Methods

Data were extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes of pancreatoduodenectomy performed for pancreatic head malignancy (29 centres in 8 countries, n=1484). Patients were grouped by their gender and the following outcomes were compared: median length of stay (LoS), 30-day readmission, 90-day mortality, unplanned return to theatre rate, provision of nutritional support rate, five-year recurrence and five-year survival.

Results

Out of 1484 patients, 56% were male and 44% were female. Median LoS was thirteen days in both sexes (p=0.4). 30-day readmission (9% vs 8%, p=0.4), 90-day mortality (both 4%, p=1.0), unplanned return to theatre (both 5%, p=0.7), provision of nutritional support (42% vs 38%), five-year recurrence (60% vs 61%, p=0.8) and five-year survival (both 32%, p=0.9) rates were all similar.

Conclusions

In our multicentre study of patients who underwent PD for malignancy, gender did not affect the studied outcomes. Gender alone should not influence patient selection.
FTP7.4 Variations in the type of nutritional support provided after pancreatoduodenectomy: results from an international multicentre retrospective cohort study
Authors: Russell Thomas , Labib Peter , Murphy Paula ,   RAW Study Collaborators, Aroori Somaiah
Published: August 2023

Aims

An early oral diet is recommended after pancreatoduodenectomy (PD), however, the nutritional management of PD patients is known to be highly variable, and some centres still provide postoperative parenteral nutrition (PN) routinely. A proportion of patients who receive PN experience clinically significant complications underscoring its judicious use. Using a multicentre cohort, this study aimed to determine the proportion of PD patients that received postoperative nutritional support (NS), describe the variations in this support, and investigate whether receiving PN correlated with morbidity.

Methods

Data was extracted from the Recurrence After Whipple’s (RAW) study database, a retrospective study of patients undergoing PD for histologically confirmed pancreatic, ampullary or distal bile duct malignancy.

Results

1323 patients (89.2%) had data on their postoperative NS status available. Of these, 45.4% received postoperative NS. This was “enteral only”, “parenteral only”, and “enteral and parenteral” in 44.3%, 35.2% and 20.5% of cases, respectively. Body mass index <18.5 kg/m2 (p=0.03), an absence of preoperative biliary stenting (p=0.009) and preoperative serum albumin <36 g/L (p=0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication (Clavien-Dindo grade ≥IIIa), one-fifth received PN.

Conclusions

Being underweight, not undergoing preoperative biliary stenting and having a low preoperative serum albumin all correlated with receiving postoperative NS. A considerable number of patients who had an uneventful recovery received PN; this should be reserved for those who are unable to take an oral diet or those in whom an oral diet is contraindicated.
Surgical experience and identification of errors in laparoscopic cholecystectomy
Authors: Humm Gemma L , Peckham-Cooper Adam , Chang Jessica , Fernandes Roland , Gomez Naim Fakih , Mohan Helen , Nally Deirdre , Thaventhiran Anthony J , Zakeri Roxanna , Gupte Anaya , Crosbie James , Wood Christopher , Dawas Khaled , Stoyanov Danail , Lovat Laurence B
Published: August 2023

Background

Surgical errors are acts or omissions resulting in negative consequences and/or increased operating time. This study describes surgeon-reported errors in laparoscopic cholecystectomy.

Methods

Intraoperative videos were uploaded and annotated on Touch SurgeryTM Enterprise. Participants evaluated videos for severity using a 10-point intraoperative cholecystitis grading score, and errors using Observational Clinical Human Reliability Assessment, which includes skill, consequence, and mechanism classifications.

Results

Nine videos were assessed by 8 participants (3 junior (specialist trainee (ST) 3–5), 2 senior trainees (ST6–8), and 3 consultants). Participants identified 550 errors. Positive relationships were seen between total operating time and error count (r2 = 0.284, P < 0.001), intraoperative grade score and error count (r2 = 0.578, P = 0.001), and intraoperative grade score and total operating time (r2 = 0.157, P < 0.001). Error counts differed significantly across intraoperative phases (H(6) = 47.06, P < 0.001), most frequently at dissection of the hepatocystic triangle (total 282; median 33.5 (i.q.r. 23.5–47.8, range 15–63)), ligation/division of cystic structures (total 124; median 13.5 (i.q.r. 12–19.3, range 10–26)), and gallbladder dissection (total 117; median 14.5 (i.q.r. 10.3–18.8, range 6–26)). There were no significant differences in error counts between juniors, seniors, and consultants (H(2) = 0.03, P = 0.987). Errors were classified differently. For dissection of the hepatocystic triangle, thermal injuries (50 in total) were frequently classified as executional, consequential errors; trainees classified thermal injuries as step done with excessive force, speed, depth, distance, time or rotation (29 out of 50), whereas consultants classified them as incorrect orientation (6 out of 50). For ligation/division of cystic structures, inappropriate clipping (60 errors in total), procedural errors were reported by junior trainees (6 out of 60), but not consultants. For gallbladder dissection, inappropriate dissection (20 errors in total) was reported in incorrect planes by consultants and seniors (6 out of 20), but not by juniors. Poor economy of movement (11 errors in total) was reported more by consultants (8 out of 11) than trainees (3 out of 11).

Conclusion

This study suggests that surgical experience influences error interpretation, but the benefits for surgical training are currently unclear.
Distribution and fixed-precision sampling plans for diamondback moth (Lepidoptera: Plutellidae), on winter–spring cabbage
Authors: Forbanka Derick Nomuh , Stemele Mxolisi Arnold , Heshula Lelethu Unathi-Nkosi Peter , Dzemo William Diymba , Kotey Daniel Ashie , Taruvinga Amon , Tshivhandekano Pfarelo Grace
Published: August 2023

The diamondback moth (Plutella xylostella L.) is the most destructive insect pest on cabbage (Brassica oleracea var. capitata L.). Infestation by this pest usually results in the indiscriminate use of insecticides by farmers due to a lack of sampling plans for this pest. Sampling plans for P. xylostella management decisions on winter–spring cabbage in the Eastern Cape Province of South Africa were developed, through population monitoring that comprised weekly counts of immature stages of P. xylostella on 60 plants for 11 wk each during the winter and spring seasons. The mean density–variance relationship was used to describe the distribution of the pest, and number of infested plants was used to develop a fixed-precision sampling plan. All plant growth stages preceding maturation were vulnerable to P. xylostella damage resulting in yield losses. A high aggregation of P. xylostella on cabbage was observed in spring than in winter. The average sample number to estimate P. xylostella density within a 15% standard error of the mean was 35 plants. Furthermore, the estimated plant proportion action threshold (AT) was 51% with density action thresholds of 0.50 and 0.80 for spring and winter, respectively. Fitting P. xylostella cumulative counts in the winter and spring sampling plans resulted in 100% and 45% reduction in insecticide treatments. The similarity of sample size and ATs between both seasons provides evidence that a single sampling plan is practical for all cabbage growing seasons. The similarity of the estimated ATs to those acceptable in established integrated pest management programs indicates reliability.
Systemic insecticides for control of stem gall wasp in highbush blueberry
Authors: DeVisser Amber K , Vandervoort Christine , Isaacs Rufus , Wise John
Published: August 2023

The gall wasp, Hemadas nubilipennis Ashmead, is a pest of highbush and lowbush blueberry and can pose a challenge to control with foliar sprays due to adult activity being during bloom and because larval development is within plant tissues. We hypothesized that systemic insecticides that move within the blueberry vascular system would reach areas where H. nubilipennis eggs are laid, causing larval mortality. Three application methods, crown injection, soil drench, and foliar spray were applied to potted ‘Jersey’ blueberry bushes at 50% and 100% rates to quantify systemic residue concentrations in shoots and leaves. Additionally, systemic insecticides were evaluated for control of gall wasps using single-shoot bioassays and measuring larval mortality at 0.01%, 0.1%, 1%, and 10% of field rate provided within a floral pick. Systemic insecticides tested in both studies included imidacloprid, flupyradifurone, and spirotetramat. The potted bush residue study determined that insecticides moved from three tested sites of entry: the roots, crown cavity, and foliage. Results from the shoot bioassays found that the mean percent larval survival of H. nubilipennis was negatively correlated with the concentration of AI detected in galls. Imidacloprid and spirotetramat were found to have the greatest potential for control of H. nubilipennis due to mortality in the shoot bioassays and similar residue concentrations in the potted bush studies to shoot bioassays. Future research should evaluate systemic insecticides applied in highbush blueberry plantings for control of H. nubilipennis using the bioassay mortality assessment method developed in this study.
The impact of functional teat number on reproductive throughput in swine
Authors: Obermier Dalton R , Howard Jeremy Thomas , Gray Kent A , Knauer Mark T
Published: August 2023

The objective was to evaluate the impact of functional teat number on reproductive throughput in swine. Data included 735 multiparous Landrace × Large White F1 females. Sow underlined traits consisted of total teat number (TT), functional teat number (FT), nonfunctional teat number (NFT), and number of functional mammary glands (FMG). Weaning traits were calculated for both the biological and the nurse dam. For the biological dam, litter size at weaning (LSW) included a sow’s biological piglets regardless of cross-fostering. For nurse dam, number weaned (NW) included the piglets a sow weaned. For the biological dam, piglet survival (PS) was calculated as litter size at weaning / (total number born × 100). Linear regression estimates were calculated in RStudio v. 1.1.456 and variance components were estimated using GIBBS3F90. Average total number born, number born alive, TT, FT, NFT, and FMG were 14.22, 13.12, 14.43, 13.96, 0.42, and 10.7, respectively. An increase in one FT enhanced (P < 0.05) LSW by 0.32 piglets and NW by 0.33 piglets. Similarly, an increase in one FT improved (P < 0.05) PS by 1.63% and reduced (P < 0.05) preweaning mortality by 2.73%. However, an increase in one FT reduced (P < 0.05) average piglet weaning weight (WW) for biological and nurse dams by 35 and 94 g, respectively. Yet an increase in one FT enhanced (P < 0.05) litter weaning weight (LWW) for biological and nurse dams by 1.3 and 1.5 kg, respectively. Heritability estimates for TT, FT, NFT, FMG, WW, LWW, LSW, and PS were 0.25, 0.22, 0.53, 0.18, 0.21, 0.22, 0.16, and 0.18, respectively. Genetic correlation estimates between FT with TT, NFT, and FMG were 0.79, 0.09, and 0.28, respectively. Estimated genetic correlations between TT with WW, LWW, LSW, and PS were 0.37, 0.38, 0.11, and −0.19, respectively. Genetic correlation estimates between FT with WW, LWW, LSW, and PS were 0.44, 0.49, 0.39, and 0.35, respectively. Results suggest increasing functional teat number would enhance both piglet survival and reproductive throughput.
Reconstruction of a Spinal Accessory Nerve Defect Using Vascularized Vastus Lateralis Motor Nerve Graft
Authors: Yanagishita Shiori , Otani Naoya , Seike Shien , Tomita Koichi , Kubo Tateki
Published: August 2023

Massive resection of a malignant tumor of the head and neck region often requires loss of critical nerves, including the spinal accessory nerve. Recently, vascularized nerve grafts (VNGs) have been used to repair facial and other nerve defects with successful outcomes, even in cases involving factors that can inhibit nerve regeneration, such as radiotherapy. However, the effectiveness of these nerve grafts against postoperative radiotherapy has yet to be explored. We report the first successful case in reconstructing a spinal accessory nerve defect after total left parotidectomy with radical neck dissection, using a vascularized vastus lateralis motor nerve graft and an anterolateral thigh flap based on the lateral circumflex femoral system, with great shoulder function outcomes even after postoperative radiotherapy. A branch of vastus lateralis motor nerve perfused by the accompanying descending branch of lateral femoral circumflex vessel was used as a nerve graft, and was repaired in an end-to-end manner. The patient underwent postoperative radiotherapy to the area of operation. At 6-months follow-up, the patient was capable of 90 degrees lateral shoulder abduction, and at 18 months, achieved full-range shoulder abduction and reported neither functional limitations of the shoulder nor complaints of any shoulder pain (Disabilities of Arm, Shoulder, and Hand score 0). Although further study is necessary to fully understand the superiority of VNGs over postoperative radiotherapy, immediate nerve reconstruction using VNG for accessory nerve defects in patients scheduled for radiotherapy postoperation may be extremely beneficial for preserving shoulder motor function and sustaining the patient’s quality of life.
Effect of intraoperative noise on postoperative pain in surgery patients under general anesthesia: Evidence from a prospective study and mouse model
Authors: You Shuai , Xu Fang , Zhu Xiwen , Qin Siyu , Zheng Xuemei , Tao Chengkun , Wu Yingcai , Chen Yupei , Shu Bin , Huang He , Duan Guangyou
Published: August 2023

Background:

Most patients are in a noisy environment during abdominal surgery under general anesthesia. This study included patients who underwent abdominal surgery under general anesthesia and established an animal model to determine whether intraoperative noise affects postoperative pain.

Materials and Methods:

This prospective study included 200 patients who underwent abdominal surgery under general anesthesia. Intraoperative noise and electroencephalograms were continuously recorded, and the mean level and time proportion of noise intensity of >70 dB were calculated. Maximum postoperative pain was assessed using a numerical rating scale (NRS) at 0–12 h and 12–24 h after surgery, and postoperative analgesia consumption in patients receiving patient-controlled intravenous analgesia was recorded. Postoperative pain intensity and electroencephalogram amplitude were compared between patients with high-noise exposure (time proportion of noise intensity greater than 70 dB ≥40%) and low-noise exposure (<40%). Mechanical pain sensitivity was tested in two groups of mice with plantar incisions exposed to 40 dB or 70–100 dB.

Results:

The time proportion of noise intensity >70 dB was identified as an independent risk factor for postoperative pain intensity (P<0.001). Pain NRS 0–12 h (4.5±1.5 vs. 3.7±1.3, P=0.001) and 12–24 h (3.9±1.5 vs. 3.2±1.1, P=0.004) after surgery in patients with high-noise exposure was significantly higher than in patients with low-noise exposure. The electroencephalogram amplitude of patients with high-noise exposure was significantly lower than that of patients with low-noise exposure (P<0.05). In the mouse model, mechanical hyperalgesia in the 70–100 dB group was significantly greater than that in the 40 dB group (P<0.001).

Conclusion:

High-level intraoperative noise exposure aggravates the degree of postoperative pain and analgesic needs of patients undergoing abdominal surgery, which may be related to the impact of noise on the neurophysiological activity of the brain and postoperative hyperalgesia.
Exploring the complex relationship between vitamin K, gut microbiota, and warfarin variability in cardiac surgery patients
Authors: Xue Ling , Singla Rajeev K. , Qin Qiong , Ding Yinglong , Liu Linsheng , Ding Xiaoliang , Qu Wenhao , Huang Chenrong , Shen Zhenya , Shen Bairong , Miao Liyan
Published: August 2023

Background and Objectives:

Due to the high individual variability of anticoagulant warfarin, this study aimed to investigate the effects of vitamin K concentration and gut microbiota on individual variability of warfarin in 246 cardiac surgery patients.

Methods:

The pharmacokinetics and pharmacodynamics (PKPD) model predicted INR and warfarin concentration. Serum and fecal samples were collected to detect warfarin and vitamin K (VK1 and menaquinone-4 (MK4)) concentrations and gut microbiota diversity, respectively. In addition, the patient’s medical records were reviewed for demographic characteristics, drug history, and CYP2C9, VKORC1, and CYP4F2 genotypes.

Results:

The PKPD model predicted ideal values of 62.7% for S-warfarin, 70.4% for R-warfarin, and 76.4% for INR. The normal VK1 level was 1.34±1.12 nmol/mL (95% CI: 0.33-4.08 nmol/mL), and the normal MK4 level was 0.22±0.18 nmol/mL (95% CI: 0.07-0.63 nmol/mL). The MK4 to total vitamin K ratio was 16.5±9.8% (95% CI: 4.3-41.5%). The S-warfarin concentration of producing 50% of maximum anticoagulation and the half-life of prothrombin complex activity tended to increase with vitamin K. Further, Prevotella and Eubacterium of gut microbiota identified as the main bacteria associated with individual variability of warfarin. The results suggest that an increase in vitamin K concentration can decrease anticoagulation, and gut microbiota may influence warfarin anticoagulation through vitamin K2 synthesis.

Conclusion:

This study highlights the importance of considering vitamin K concentration and gut microbiota when prescribing warfarin. The findings may have significant implications for the personalized use of warfarin. Further research is needed to understand better the role of vitamin K and gut microbiota in warfarin anticoagulation.
Anticoagulation prescription among atrial fibrillation patients managed with and without an anticoagulant initiation pathway: a cohort study
Authors: Carter Jaimee , Kirwan Christopher , Niaz Saghar , Baweja Shriya , Al-Haimus Fayad , Hu Yang , Ramsden Sophie , Clayton Natasha , de Wit Kerstin
Published: August 2023

Background and importance

The Canadian Association of Emergency Physicians atrial fibrillation (AF) checklist advises that emergency physicians initiate anticoagulation therapy for patients with AF or flutter who are CHADS65 positive.

Objectives

The aim was to compare anticoagulation initiation rates between patients treated with and without an anticoagulation assessment pathway (the SAFE pathway).

Design

This was a retrospective cohort study.

Settings and participants

All emergency department patients were discharged home with a diagnosis of AF between June 2018 and May 2020 at two Canadian emergency departments.

Intervention

The SAFE pathway is a hard copy form which allows emergency physicians to document contraindications to anticoagulation, the positive components of the CHADS65 score, and details how to prescribe anticoagulation.

Outcome measures and analysis

Trained researchers abstracted data on the use of the SAFE pathway by the presence or absence of the completed, scanned pathway in the electronic medical chart. The exposure of interest was use of this pathway. Patients were followed forward in time for 90 days by electronic medical record review to document stroke, transient ischemic attack, arterial embolism and major bleeding events. All events were independently adjudicated. Adjusted odds ratios were calculated to compare outcomes between those managed with and without the SAFE pathway.

Results

In total, 766 patients were included, of whom 264 were already taking anticoagulation, 166 were CHADS65 negative and 65 had a contraindication to anticoagulation, leaving 271 patients eligible for anticoagulation prescription. Among the 271 eligible patients, 137/166 managed with the SAFE pathway were initiated on anticoagulation and 24/105 managed without the SAFE pathway started anticoagulation (adjusted odds ratio 25.9; 13.1–51.2). There was no statistically significant difference in the 90-day rate of stroke or bleeding.

Conclusion

Use of the SAFE pathway was associated with a higher rate of anticoagulation prescription.
A genetic variation in Fucosyltransferase 8 accelerates HIV-1 disease progression indicating a role for N-glycan fucosylation
Authors: van Pul Lisa , Maurer Irma , Boeser-Nunnink Brigitte D.M. , Harskamp Agnes M. , van Dort Karel A. , Kootstra Neeltje A.
Published: August 2023

Objectives:

Core fucosylation by fucosyltransferase 8 (FUT8) is an important post-translational modification that impacts components of the immune system. Genetic variations in FUT8 can alter its function and could therefore play a role in the anti-viral immune response and pathogenesis of HIV-1. This study analyzed the effect of a single nucleotide polymorphism (SNP) in FUT8 on the clinical course of HIV-1 infection.

Design/methods:

The effect of SNPs in FUT8 on untreated HIV-1 disease outcome were analyzed in a cohort of 304 people with HIV-1 (PWH) using survival analysis. Flow-cytometry was used to determine the effect of SNP on T-cell activation, differentiation and exhaustion/senescence. T-cell function was determined by proliferation assay and by measuring intracellular cytokine production. The effect of the SNP on HIV-1 replication was determined by in-vitro HIV-1 infections. Sensitivity of HIV-1 produced in PBMC with or without the SNP to broadly neutralizing antibodies was determined using a TZM-bl based neutralization assay.

Results:

Presence of the minor allele of SNP rs4131564 was associated with accelerated disease progression. The SNP had no effect on T-cell activation and T cell differentiation in PWH. Additionally, no differences in T cell functionality as determined by proliferation and cytokine production was observed. HIV-1 replication and neutralization sensitivity was also unaffected by the SNP in FUT8.

Conclusions:

SNP rs4131564 in FUT8 showed a major impact on HIV-1 disease course underscoring a role for N-glycan fucosylation even though no clear effect on the immune system or HIV-1 could be determined in vitro.
Quantitative Assessment of the Effects of Botulinum Toxin on Skin Perfusion by Laser Doppler Flowmetry: A Clinical Trial
Authors: Balik Ozan
Published: August 2023

Several studies reported an increase in skin glow, pore shrinkage, and an improvement in oily skin with its mesobotox-like use. The authors aimed to determine the extent of late changes in skin perfusion in the superficial dermis when Botulinium toxin A (Btx-A) is injected into the skin with mesotherapy, independent of any stimulant and surgery, using a laser Doppler flowmeter for analysis. Btx-A was applied to the right cheek and saline mesotherapy to the left cheeks of a total of 9 subjects. Two weeks later, their contribution to skin circulation was measured by the laser Doppler flowmeter. Although it was more on the side where Btx-A was applied, an increase in vascularity was observed on both sides of the subjects and no statistical difference could be found between the right and left cheeks in the late period.
Can mass drug administration of moxidectin accelerate onchocerciasis elimination in Africa?
Authors: Kura Klodeta , Milton Philip , Hamley Jonathan I. D. , Walker Martin , Bakajika Didier K. , Kanza Eric M. , Opoku Nicholas O. , Howard Hayford , Nigo Maurice M. , Asare Sampson , Olipoh George , Attah Simon K. , Mambandu Germain L. , Kennedy Kambale Kasonia , Kataliko Kambale , Mumbere Mupenzi , Halleux Christine M. , Hopkins Adrian , Kuesel Annette C. , Kinrade Sally , Basáñez Maria-Gloria
Published: August 2023

Epidemiological and modelling studies suggest that elimination of
Onchocerca volvulus
transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of
O. volvulus
microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA.

This article is part of the theme issue ‘Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Modelling morbidity for neglected tropical diseases: the long and winding road from cumulative exposure to long-term pathology
Authors: Borlase Anna , Prada Joaquin M. , Crellen Thomas
Published: August 2023

Reducing the morbidities caused by neglected tropical diseases (NTDs) is a central aim of ongoing disease control programmes. The broad spectrum of pathogens under the umbrella of NTDs lead to a range of negative health outcomes, from malnutrition and anaemia to organ failure, blindness and carcinogenesis. For some NTDs, the most severe clinical manifestations develop over many years of chronic or repeated infection. For these diseases, the association between infection and risk of long-term pathology is generally complex, and the impact of multiple interacting factors, such as age, co-morbidities and host immune response, is often poorly quantified. Mathematical modelling has been used for many years to gain insights into the complex processes underlying the transmission dynamics of infectious diseases; however, long-term morbidities associated with chronic or cumulative exposure are generally not incorporated into dynamic models for NTDs. Here we consider the complexities and challenges for determining the relationship between cumulative pathogen exposure and morbidity at the individual and population levels, drawing on case studies for trachoma, schistosomiasis and foodborne trematodiasis. We explore potential frameworks for explicitly incorporating long-term morbidity into NTD transmission models, and consider the insights such frameworks may bring in terms of policy-relevant projections for the elimination era.

This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Lymphatic filariases and soil-transmitted helminthiases in Sri Lanka: the challenge of eliminating residual pockets of transmission
Authors: Chandrasena Nilmini T. G. A. , Gunaratna I. E. , Ediriweera Dileepa , de Silva N. R.
Published: August 2023

Sri Lanka has successfully met the challenge of controlling both lymphatic filariasis (LF) and soil-transmitted helminthiases (STH) as public health problems. The primary public health strategy for combatting both conditions has been preventive chemotherapy. The national programme for the elimination of LF implemented five annual rounds of mass chemotherapy in the endemic districts from 2002 to 2006 using a combination of diethylcarbamazine and albendazole. The overall microfilaria rate declined from 0.21% in 2001 before the mass chemotherapy, to 0.06% in 2016, at declaration of elimination of LF as a public health problem by the World Health Organization. Currently Sri Lanka is in the phase of post-validation surveillance. Achieving control of STH has been more difficult. Mass deworming programmes have been implemented for nearly a century, and national-level surveys reported prevalence rates declining from 6.9% in 2003 to 1% in 2017. However, neither of these infections has been completely eliminated. A situation analysis indicates continued transmission of both among high-risk communities. This paper explores the reasons for persistence of transmission of both LF and STH in residual pockets and the measures that are required to achieve long-term control, or perhaps even interrupt transmission in Sri Lanka.

This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
A positive consequence of the COVID-19 pandemic: how the counterfactual experience of school closures is accelerating a multisectoral response to the treatment of neglected tropical diseases
Authors: Bundy Donald A. P. , Schultz Linda , Antoninis Manos , Barry Fatoumata B. M. , Burbano Carmen , Croke Kevin , Drake Lesley , Gyapong John , Karutu Carol , Kihara Jimmy , Lo Mouhamadou Moustapha , Makkar Prerna , Mwandawiro Charles , Ossipow Suzy J. , Bento Ana Ramos , Rollinson David , Shah Hemang , Turner Hugo C.
Published: August 2023

Global access to deworming treatment is one of the public health success stories of low-income countries in the twenty-first century. Parasitic worm infections are among the most ubiquitous chronic infections of humans, and early success with mass treatment programmes for these infections was the key catalyst for the neglected tropical disease (NTD) agenda. Since the launch of the ‘London Declaration’ in 2012, school-based deworming programmes have become the world's largest public health interventions. WHO estimates that by 2020, some 3.3 billion school-based drug treatments had been delivered. The success of this approach was brought to a dramatic halt in April 2020 when schools were closed worldwide in response to the COVID-19 pandemic. These closures immediately excluded 1.5 billion children not only from access to education but also from all school-based health services, including deworming. WHO Pulse surveys in 2021 identified NTD treatment as among the most negatively affected health interventions worldwide, second only to mental health interventions. In reaction, governments created a global Coalition with the twin aims of reopening schools and of rebuilding more resilient school-based health systems. Today, some 86 countries, comprising more than half the world's population, are delivering on this response, and school-based coverage of some key school-based programmes exceeds those from January 2020. This paper explores how science, and a combination of new policy and epidemiological perspectives that began in the 1980s, led to the exceptional growth in school-based NTD programmes after 2012, and are again driving new momentum in response to the COVID-19 pandemic.

This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Global prioritization of endemic zoonotic diseases for conducting surveillance in domestic animals to protect public health
Authors: Qiu Yu , Guitian Javier , Webster Joanne P. , Musallam Imadidden , Haider Najmul , Drewe Julian A. , Song Junxia
Published: August 2023

Zoonotic diseases (zoonoses) originating from domestic animals pose a significant risk to people's health and livelihoods, in addition to jeopardizing animal health and production. Effective surveillance of endemic zoonoses at the animal level is crucial to assessing the disease burden and risk, and providing early warning to prevent epidemics in animals and spillover to humans. Here we aimed to prioritize and characterize zoonoses for which surveillance in domestic animals is important to prevent human infections at a global scale. A multi-criteria qualitative approach was used, where disease-specific information was obtained across literature of the leading international health organizations. Thirty-two zoonoses were prioritized, all of which have multi-regional spread, cause unexceptional human infections and have domestic animal hosts as important sources or sentinels of zoonotic infections. Most diseases involve multiple animal hosts and/or modes of zoonotic transmission, where a lack of specific clinical signs in animals further complicates surveillance. We discuss the challenges of animal health surveillance in endemic and resource-limited settings, as well as potential avenues for improvement such as the multi-disease, multi-sectoral and digital surveillance approaches. Our study will support global capacity-building efforts to strengthen the surveillance and control of endemic zoonoses at their animal sources.

This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Determinants of Bluetooth-enabled Self Measured Blood Pressure monitoring in Federally Qualified Health Centers
Authors: Hellem Abby , Whitfield Candace , Mansour Maria , Curran Yvonne , Dinh Mackenzie , Warden Kimberly , Skolarus Lesli
Published: August 2023

Background

In 2021, the Health Resources and Services Administration (HRSA) launched the National Hypertension Control Initiative (HTN Initiative) with the goal to enhance HTN control through Bluetooth-enabled self-measured blood pressure (BT SMBP) monitoring and use this data to inform clinical decisions in Federally Qualified Health Centers (FQHCs) with large proportion of their population with uncontrolled BP. We sought to understand the experience of Michigan-based FQHCs in implementing the HTN initiative.

Methods

Staff from three Michigan-based FQHCs were invited to participate in semi-structured interviews from September to November 2022. Interviews were conducted in-person and were based on the Tailored Implementation of Chronic Diseases framework. Content analysis was performed by three coders.

Results

Ten staff participated in interviews (FQHC 1: n=6, FQHC 2: n=1, FQHC 3: n=3). The FQHCs differed in their stage of implementation and their approach. FQHC 1 created a large-scale, community health worker driven program, FQHC 2 created a small-scale, short term, BP device loan program, and FQHC 3 created a primarily outsourced, large-scale program through a contracted partner. Positive staff attitudes and outcome expectations, previous experience with SMBP grants, and supportive clinic leadership were identified as facilitators to implementation; Patients high social needs, SMBP-related Technology, and insufficient workforce and staff capacity were identified as barriers.

Conclusion

BT SMBP among FQHC patients is promising but challenges in integrating SMBP data into clinic workflow, workforce capacity to support the high social needs of participants and to assist in reacting to the more frequent BP data remain to be overcome.
Trigeminal innervation and tactile responses in mouse tongue
Authors: Zhang Linghua , Nagel Maximilian , Olson William P , Chesler Alexander T. , O’Connor Daniel H.
Published: August 2023

The mammalian tongue is richly innervated with somatosensory, gustatory and motor fibers. These form the basis of many ethologically important functions such as eating, speaking and social grooming. Despite its high tactile acuity and sensitivity, the neural basis of tongue mechanosensation remains largely mysterious. Here we explored the organization of mechanosensory afferents in the tongue and found that each lingual papilla is innervated by Piezo2+trigeminal neurons. Notably, each fungiform papilla contained highly specialized ring-like sensory neuron terminations that asymmetrically circumscribe the taste buds. Myelinated lingual afferents in the mouse lingual papillae did not form corpuscular sensory end organs but rather had only free nerve endings.In vivosingle-unit recordings from the trigeminal ganglion revealed lingual low-threshold mechanoreceptors (LTMRs) with conduction velocities in the Aδ range or above and distinct adaptation properties ranging from intermediately adapting (IA) to rapidly adapting (RA). IA units were sensitive to both static indentation and stroking, while RA units had a preference for tangential forces applied by stroking. Lingual LTMRs were not directly responsive to rapid cooling or chemicals that can induce astringent or numbing sensations. Sparse labeling of lingual afferents in the tongue revealed distinct terminal morphologies and innervation patterns in fungiform and filiform papillae. Together, our results indicate that fungiform papillae are mechanosensory structures, while suggesting a simple model that links the functional and anatomical properties of tactile sensory neurons in the tongue.
Deep Learning Enhanced Tandem Repeat Variation Identification via Multi-Modal Conversion of Nanopore Reads Alignment
Authors: Liao Xingyu , Zhou Juexiao , Zhang Bin , Xu Xiaopeng , Li Haoyang , Gao Xin
Published: August 2023

Identification of tandem repeat (TR) variations plays a crucial role in advancing our understanding of genetic diseases, forensic analysis, evolutionary studies, and crop improvement, thereby contributing to various fields of research and practical applications. However, traditional TR identification methods are often limited to processing genomes obtained through sequence assembly and cannot directly start detection from sequencing reads. Furthermore, the inflexibility of detection mode and parameters hinders the accuracy and completeness of the identification, rendering the results unsatisfactory. These shortcomings result in existing TR variation identification methods being associated with high computational cost, limited detection sensitivity, precision and comprehensiveness. Here, we propose DeepTRs, a novel method for identifying TR variations, which enables direct TR variation identification from raw Nanopore sequencing reads and achieves high sensitivity, accuracy, and completeness results through the multi-modal conversion of Nanopore reads alignment and deep learning. Comprehensive evaluations demonstrate that DeepTRs outperform existing methods.