bluuebunny/crossref_metadata_2025 huggingface dataset:
MCANet: shared-weight-based MultiheadCrossAttention network for drug–target interaction prediction
Authors: Bian Jilong , Zhang Xi , Zhang Xiying , Xu Dali , Wang Guohua
Published: March 2023

Accurate and effective drug–target interaction (DTI) prediction can greatly shorten the drug development lifecycle and reduce the cost of drug development. In the deep-learning-based paradigm for predicting DTI, robust drug and protein feature representations and their interaction features play a key role in improving the accuracy of DTI prediction. Additionally, the class imbalance problem and the overfitting problem in the drug–target dataset can also affect the prediction accuracy, and reducing the consumption of computational resources and speeding up the training process are also critical considerations. In this paper, we propose shared-weight-based MultiheadCrossAttention, a precise and concise attention mechanism that can establish the association between target and drug, making our models more accurate and faster. Then, we use the cross-attention mechanism to construct two models: MCANet and MCANet-B. In MCANet, the cross-attention mechanism is used to extract the interaction features between drugs and proteins for improving the feature representation ability of drugs and proteins, and the PolyLoss loss function is applied to alleviate the overfitting problem and the class imbalance problem in the drug–target dataset. In MCANet-B, the robustness of the model is improved by combining multiple MCANet models and prediction accuracy further increases. We train and evaluate our proposed methods on six public drug–target datasets and achieve state-of-the-art results. In comparison with other baselines, MCANet saves considerable computational resources while maintaining accuracy in the leading position; however, MCANet-B greatly improves prediction accuracy by combining multiple models while maintaining a balance between computational resource consumption and prediction accuracy.
RNAget: an API to securely retrieve RNA quantifications
Authors: Upchurch Sean , Palumbo Emilio , Adams Jeremy , Bujold David , Bourque Guillaume , Nedzel Jared , Graham Keenan , Kagda Meenakshi S , Assis Pedro , Hitz Benjamin , Righi Emilio , Guigó Roderic , Wold Barbara J ,   GA4GH RNA-Seq Task Team, Adams Jeremy , Brazma Alvis , Bujold David , Burchard Julia , Capka Joe , Cherry Michael , Clarke Laura , Craft Brian , Dermitzakis Manolis , Diekhans Mark , Dursi John , Fitzsimons Michael Sean , Flaming Zac , Garrido Romina , Gil Alfred , Godden Paul , Green Matt , Guigo Roderic , Guttman Mitch , Haas Brian , Haeussler Max , Hitz Benjamin , Li Bo , Linnarsson Sten , Lipski Adam , Liu David , Longerich Simonne , Lougheed David , Manning Jonathan , Marioni John , Meyer Christopher , Montgomery Stephen , Morrow Alyssa , Munoz-Power Fuentes Alfonso , Nedzel Jared , Nguyen David , Osborn Kevin , Ouellette Francis , Palumbo Emilio , Papatheodorou Irene , Pervouchine Dmitri , Ramani Arun , Rambla Jordi , Sadjad Bashir , Steinberg David , Talkar Jeremiah , Tickle Timothy , Tzeng Kathy , Upchurch Sean , Vaisipour Saman , Watford Sean , Wold Barbara , Zhang Zhenyu , Zhu Jing
Published: March 2023

Large-scale sharing of genomic quantification data requires standardized access interfaces. In this Global Alliance for Genomics and Health project, we developed RNAget, an API for secure access to genomic quantification data in matrix form. RNAget provides for slicing matrices to extract desired subsets of data and is applicable to all expression matrix-format data, including RNA sequencing and microarrays. Further, it generalizes to quantification matrices of other sequence-based genomics such as ATAC-seq and ChIP-seq.

Availability and implementation

https://ga4gh-rnaseq.github.io/schema/docs/index.html.
Signalling on islands: the case of Lilford’s wall lizard (Podarcis lilfordi gigliolii) from Dragonera
Authors: de La Cruz Ferran , Pérez i de Lanuza Guillem , Font Enrique
Published: March 2023

Studies of the effects of insularity on animal signals are scarce, particularly in lizards. Here, we use Lilford’s wall lizard from Dragonera (Podarcis lilfordi gigliolii) to ask how island conditions have affected its repertoire of social signals, focusing on two visual signals shared by many Podarcis species: ultraviolet (UV)–blue-reflecting ventrolateral colour patches and visual displays. We examined whether the number or spectral characteristics of the UV–blue patches are associated with traits related to individual quality. We also used visual models to assess visual conspicuousness and to measure sexual dichromatism. We did not observe foot shakes or any other visual displays usually found in continental Podarcis. We found that none of the UV–blue patch variables covaried with morphometric variables indicative of fighting ability or body condition in males, suggesting that this coloration does not signal individual quality. We also found very little sexual dichromatism. In particular, the UV–blue patches of females seem over-expressed and more similar to those of males than those of continental Podarcis. Ancestral state reconstruction reveals that the lack of sexual dimorphism in the UV–blue patches is a derived condition for P. lilfordi gigliolii and other Podarcis living on small islands. Our results thus show a pattern of reduced social signalling in P. lilfordi gigliolii relative to mainland Podarcis, with some signals being lost or under-expressed (visual displays) and others losing their signalling function (UV–blue patches). We hypothesize that these changes are attributable to the high population density of P. lilfordi gigliolii, which discourages territorial behaviour and promotes extreme social tolerance, making most social signals unnecessary. More work will be needed to determine whether this is a common pattern in lizards inhabiting small and densely populated islands.
Early differentiation and gene expression characteristics of trophoblast lineages
Authors: Qin Jiaying , Li Wanqiong , Lv Bo , Xue Zhigang , Xue Jinfeng
Published: March 2023

With the development of the embryo, the totipotent blastomere undergoes the first lineage decision to the inner cell mass (ICM) and the trophectoderm (TE). The ICM forms the fetus while the TE forms the placenta, which is one of the unique organs in mammals serving as the interface between maternal and fetal bloodstreams. Proper trophoblast lineage differentiation is crucial for correct placental and fetal development, including the TE progenitor self-renewal and its differentiation toward mononuclear cytotrophoblast, which later either develops into invasive extravillous trophoblast, remodeling the uterine vascular, or fuses into multinuclear syncytiotrophoblast, secreting pregnancy-sustaining hormone. Aberrant differentiation and gene expression of trophoblast lineage is associated with severe pregnancy disorders and fetal growth restriction. This review focuses on the early differentiation and key regulatory factors of trophoblast lineage, which have been poorly elucidated. Meanwhile, the recent development of trophoblast stem cells, trophectoderm stem cells, and blastoids derived from pluripotent stem cells bring the accessible model to investigate the profound mystery of embryo implantation and placentation and were also summarized.
Tau-mediated axonal degeneration is prevented by activation of the WldS pathway
Authors: Stubbs Katy , Batchelor Ben , Sivanantharajah Lovesha , Sealey Megan , Ramirez-Moreno Miguel , Ruiz Eva , Richardson Brad , Perry Victor H , Newman Tracey A , Mudher Amritpal
Published: March 2023

Tauopathy is characterized by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule-associated protein tau. The neuronal changes evident in tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (WldS) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by co-expression of WldS. In a Drosophila model of tauopathy in which expression of human 0N3R tau protein leads to progressive age-dependent phenotypes, WldS was expressed with and without activation of the downstream pathway. The olfactory receptor neuron circuit OR47b was used for these studies in adults, and the larval motor neuron system was employed in larvae. Tau phenotypes studied included neurodegeneration, axonal transport, synaptic deficits and locomotor behaviour. Impact on total tau was ascertained by assessing total, phosphorylated and misfolded tau levels by immunohistochemistry. Activation of the pathway downstream of WldS completely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of WldS was activated several weeks after tau-mediated degeneration had become established. Though total tau levels were not altered, the protected neurons displayed significantly reduced MC1 immunoreactivity suggestive of clearance of misfolded tau, as well as a trend for a decline in tau species phosphorylated at the AT8 and PHF1 epitopes. In contrast, WldS expression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in tau-expressing larvae. This collectively implies that the pathway mediating the protective effect of WldS intersects with the mechanism(s) of degeneration initiated by tau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.
B lymphocyte responses in Parkinson’s disease and their possible significance in disease progression
Authors: Scott Kirsten M , Chong Yen Ting , Park Seoyoung , Wijeyekoon Ruwani S , Hayat Shaista , Mathews Rebeccah J , Fitzpatrick Zachary , Tyers Pam , Wright Georgia , Whitby Jennifer , Barker Roger A , Hu Michele T , Williams-Gray Caroline H , Clatworthy Menna R
Published: March 2023

Inflammation contributes to Parkinson’s disease pathogenesis. We hypothesized that B lymphocytes are involved in Parkinson’s disease progression. We measured antibodies to alpha-synuclein and tau in serum from patients with rapid eye movement sleep behaviour disorder (n = 79), early Parkinson’s disease (n = 50) and matched controls (n = 50). Rapid eye movement sleep behaviour disorder cases were stratified by risk of progression to Parkinson’s disease (low risk = 30, high risk = 49). We also measured B-cell activating factor of the tumour necrosis factor receptor family, C-reactive protein and total immunoglobulin G. We found elevated levels of antibodies to alpha-synuclein fibrils in rapid eye movement sleep behaviour disorder patients at high risk of Parkinson’s disease conversion (ANOVA, P < 0.001) and lower S129D peptide-specific antibodies in those at low risk (ANOVA, P < 0.001). An early humoral response to alpha-synuclein is therefore detectable prior to the development of Parkinson’s disease. Peripheral B lymphocyte phenotyping using flow cytometry in early Parkinson’s disease patients and matched controls (n = 41 per group) revealed reduced B cells in Parkinson’s disease, particularly in those at higher risk of developing an early dementia [t(3) = 2.87, P = 0.01]. Patients with a greater proportion of regulatory B cells had better motor scores [F(4,24) = 3.612, P = 0.019], suggesting they have a protective role in Parkinson’s disease. In contrast, B cells isolated from Parkinson’s disease patients at higher risk of dementia had greater cytokine (interleukin 6 and interleukin 10) responses following in vitro stimulation. We assessed peripheral blood lymphocytes in alpha-synuclein transgenic mouse models of Parkinson’s disease: they also had reduced B cells, suggesting this is related to alpha-synuclein pathology. In a toxin-based mouse model of Parkinson’s disease, B-cell deficiency or depletion resulted in worse pathological and behavioural outcomes, supporting the conclusion that B cells play an early protective role in dopaminergic cell loss. In conclusion, we found changes in the B-cell compartment associated with risk of disease progression in rapid eye movement sleep behaviour disorder (higher alpha-synuclein antibodies) and early Parkinson’s disease (lower levels of B lymphocytes that were more reactive to stimulation). Regulatory B cells play a protective role in a mouse model, potentially by attenuating inflammation and dopaminergic cell loss. B cells are therefore likely to be involved in the pathogenesis of Parkinson’s disease, albeit in a complex way, and thus warrant consideration as a therapeutic target.
Effect of hydrogen impurities on hydrogen oxidation activity of Pt/C catalyst in proton exchange membrane fuel cells
Authors: Qin Yufeng , Sun Chaoyong , Ke Shaojie , Wen Rou , Wang Yifan , Ji Jing , Dou Meiling
Published: March 2023

High-purity of hydrogen is vital to the guarantee of end usage in proton exchange membrane fuel cell (PEMFC) electric vehicles (EVs) with superior durability and low expense. However, the currently employed hydrogen, primarily from fossil fuel, still contains some poisoning impurities that significantly affect the durability of PEMFCs. Here, we investigate the poisoning effect of several typical hydrogen impurities (S2–, Cl–, HCOO– and CO32–) on the hydrogen oxidation reaction (HOR) of the state-of-the-art carbon-supported platinum (Pt/C) catalyst used in the PEMFC anode. Electrochemical results indicate that the electrochemically active surface area of Pt/C is hampered by these hydrogen impurities with reduced effective Pt reactive sites due to the competitive adsorption against hydrogen at Pt sites showing the extent of the poisoning on Pt sites in the order: S2– > Cl– > HCOO– > CO32–. Density functional theory calculations reveal that the adsorption energy of S2– on Pt (111) is greater than that of Cl–, HCOO– and CO2, and the electronic structure of Pt is found to be changed due to the adsorption of impurities showing the downshift of the d-band centre of Pt that weakens the adsorption of hydrogen on the Pt sites. This work provides valuable guidance for future optimization of hydrogen quality and also emphasizes the importance of anti-poisoning anode catalyst development, especially towards H2S impurities that seriously affect the durability of PEMFCs.
Integrated energy corridor: a comprehensive proposal of the low-carbon transition for China Energy Group
Authors: Gao Min , Nan Haiming , Ren Haijun , Liu Yonggang , Wang Lizhi , Xu Zhaoyang , Zhao Pengfei
Published: March 2023

New energy is considered to be an indispensable means to significantly reduce carbon emissions and to achieve the temperature-control goals defined by the Paris Climate Accord. Despite the bright future, the inherent characteristics, including volatility, intermittency and uneven seasonal and geographical distributions, and the rapid growth of installations make it increasingly difficult to connect green electricity to grids. This becomes a dominating bottleneck for the low-carbon transition of China Energy Group (CE). This paper aims to help with the implementation of the new-energy development plan and to define the low-carbon energy-transition path for CE. Based on the current industry structure of CE, Shenhua Engineering Technology Co., Ltd proposes the concept of an ‘integrated energy corridor’. The integrated energy corridor represents a comprehensive energy-transmission channel with coal, green electricity, green hydrogen, green oxygen and other green energy products such as transmission media, railways, pipelines and power grids as transmission means and thermal power, coal chemical plants, cities, etc. along the route as new-energy consumers and regulators. The integrated energy corridor can support the rapid development of new-energy assets and the low-carbon transition of CE.
Microneedling-associated facial skin changes
Authors: Baptista Gonçalves Rui , Taibjee Saleem , Ferguson Janice , Coulson Ian H
Published: March 2023

A 28-year-old Afro-Caribbean woman underwent a second facial microneedling procedure to improve skin texture. A skin cleanser was applied pretreatment. The next day she had a sensation of irritation and tingling in the treated areas and within 3 days had developed red inflamed nodules on both cheeks.
PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation
Authors: Pezhman Laleh , Hopkin Sophie J , Begum Jenefa , Heising Silke , Nasteska Daniela , Wahid Mussarat , Ed Rainger G , Hodson David J , Iqbal Asif J , Chimen Myriam , McGettrick Helen M
Published: March 2023

Dysregulation of leukocyte trafficking, lipid metabolism, and other metabolic processes are the hallmarks that underpin and drive pathology in obesity. Current clinical management targets alternations in lifestyle choices (e.g. exercise, weight loss) to limit the impact of the disease. Crucially, re-gaining control over the pathogenic cellular and molecular processes may offer an alternative, complementary strategy for obese patients. Here we investigate the impact of the immunopeptide, PEPITEM, on pancreas homeostasis and leukocyte trafficking in mice on high-fed obesogenic diet (HFD). Both prophylactic and therapeutic treatment with PEPITEM alleviated the effects of HFD on the pancreas, reducing pancreatic beta cell size. Moreover, PEPITEM treatment also limited T-cell trafficking (CD4+ T-cells and KLRG1+ CD3+ T-cells) to obese visceral, but not subcutaneous, adipose tissue. Similarly, PEPITEM treatment reduced macrophage numbers within the peritoneal cavity of mice on HFD diet at both 6 and 12 weeks. By contrast, PEPITEM therapy elevated numbers of T and B cells were observed in the secondary lymphoid tissues (e.g. spleen and inguinal lymph node) when compared to the untreated HFD controls. Collectively our data highlights the potential for PEPITEM as a novel therapy to combat the systemic low-grade inflammation experienced in obesity and minimize the impact of obesity on pancreatic homeostasis. Thus, offering an alternative strategy to reduce the risk of developing obesity-related co-morbidities, such as type 2 diabetes mellitus, in individuals at high risk and struggling to control their weight through lifestyle modifications.
An efficiently working brain characterizes higher mental flow that elicits pleasure in Chinese calligraphic handwriting
Authors: Wang Yue , Han Buxin , Li Min , Li Juan , Li Rui
Published: March 2023

The mental flow that commonly emerges during immersion in artistic activities is beneficial for maintaining mental health. However, there is not that much converging neurobiological evidence about how flow emerges and elicits pleasure in arts. Using an imitation task of Chinese calligraphic handwriting with self-rated subjective flow experience, we investigated the neural interactions supporting flow. Our results show that calligraphic handwriting requires cooperation between widespread multimodal regions that span the visual and sensorimotor areas along the dorsal stream, the top-down attentional control system, and the orbito-affective network. We demonstrate that higher flow is characterized by an efficiently working brain that manifests as less activation particularly in the brain regions within dorsal attention network and functional connectivity between visual and sensorimotor networks in calligraphy. Furthermore, we also propose that pleasure during calligraphy writing arises from efficient cortical activity in the emergence of flow, and the orbito-caudate circuit responsible for feelings of affection. These findings provide new insight into the neuropsychological representations of flow through art, and highlight the potential benefits of artistic activities to boost well-being and prosperity.
A Simple HPTLC Approach of Quantification of Serratol and Tirucallic Acid with Boswellic Acids in Boswellia serrata by Validated Densitometric Method with MS/MS Characterization
Authors: Mukadam Smruti , Ghule Chetana , Girme Aboli , Shinde Vaibhav M , Hingorani Lal , Mahadik Kakasaheb R
Published: March 2023

This study was planned to develop a simple high-performance thin-layer chromatography method for qualitative and quantitative estimation of 3-acetyl-11-keto-β-boswellic acid (AKBBA), β-boswellic acid (BBA), 3-oxo-tirucallic acid (TCA) and serratol (SRT) with HPTLC-ESI-MS/MS for characterization in Boswellia serrata Roxb. oleo gum resin extract. The method was developed with hexane-ethyl acetate-toluene-chloroform-formic acid as mobile phase. RF values observed for AKBBA, BBA, TCA and SRT were 0.42, 0.39, 0.53 and 0.72, respectively. The method was validated according to International Council for Harmonisation guidelines. The concentration range for linearity was 100–500 ng/band for AKBBA and 200–700 ng/band for the other three markers with r2 > 0.99. The method resulted in good recoveries as 101.56, 100.68, 98.64 and 103.26%. The limit of detection was noticed as 25 , 37, 54 and 38 ng/band, with a limit of quantification as 76, 114, 116 and 115 ng/band, for AKBBA, BBA, TCA and SRT, respectively. The four markers were identified and confirmed in B. serrata extract using TLC-MS by indirect profiling by LC-ESI-MS/MS and were identified as terpenoids, TCA and cembranoids: AKBBA (mass/charge (m/z) = 513.00), BBA (m/z = 455.40), 3-oxo-tirucallic acid (m/z = 455.70) and SRT (m/z = 291.25), respectively.
Far From Home: The Role of Travel Distance and Care Fragmentation in Surgical Outcomes for Inflammatory Bowel Disease
Authors: Booth Alexander , Colorado Henry , Magwood Gayenell , Forster Erin , Axon Robert N , Curran Thomas
Published: March 2023

Background

Fragmented care for inflammatory bowel disease (IBD) is known to correlate negatively with outcomes, but it is unclear which aspects of care fragmentation are relevant and potentially modifiable. Furthermore, there is little data on the relationship between travel distance and the benefits of integrated care models. Hypothesizing care coordination in the preoperative period may have a significant impact on surgical outcomes, we explored associations between integrated care, travel distance, and surgical outcomes.

Methods

A single-center retrospective cohort study of patients undergoing index abdominal surgery was done to compare the rate of surgical complications with and without long travel distance and nonintegrated preoperative care. Multivariable logistic regression was used to identify factors independently associated with complications.

Results

One hundred and fifty-seven patients were included. Complications were more common among patients with travel distance >75 miles (47.6% vs 27.4%, P = .012). Integrated preoperative care was not significant on bivariate (P = .381) or multivariable analysis but had a stronger association among patients with travel distance <75 miles (20.9% integrated vs 36.7%, P = .138). After adjustment, new ileostomy, open surgical approach, and distance >75 miles were independently associated with complications.

Conclusions

Patients with longer travel distances to the hospital were twice as likely to have a surgical complication after adjusting for other risk factors. Without significant accommodations for remote patients, potential benefits of an integrated model for IBD care may be limited to patients who live close to the medical center. Future efforts addressing continuity of care should consider tactics to mitigate the impact of travel distance on outcomes.
Acute asymptomatic hyponatraemia following inpatient initiation of angiotensin receptor–neprilysin inhibitor: a case report
Authors: Dean John-Henry L , Patel Mayank P , Corpuz Elaine , Cahill Michael S , Fentanes Emilio
Published: March 2023

Background

Utilization of sacubitril/valsartan is increasing as a component of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Common adverse effects associated with the medication such as hypotension and hyperkalaemia have been described; however, hyponatraemia is very rarely reported to have a potential association with use of the medication. In this report, we describe what we believe to be the first reported case of acute hyponatraemia likely attributable to inpatient initiation of sacubitril/valsartan.

Case Summary

A 71-year-old female presented with 2 weeks of progressively worsening dyspnoea and orthopnoea. Bedside echocardiography identified a dilated cardiomyopathy with an estimated left ventricular ejection fraction <30% and diffuse hypokinesis, and given the associated clinical syndrome, she was diagnosed with heart failure with reduced ejection fraction. In conjunction with diuresis, guideline-directed medical therapy was initiated. She developed acute worsening of her previously mild hyponatraemia shortly after starting sacubitril/valsartan, and this improved following discontinuation of the medication. She was subsequently able to tolerate losartan while maintaining eunatraemia, and her ejection fraction improved to 46% on repeat imaging.

Discussion

Angiotensin receptor–neprilysin inhibitors are an integral component of guideline-directed medical therapy with proven benefits for patients with heart failure with reduced ejection fraction. Although the association between use of these medications and hyponatraemia appears to be exceedingly rare, clinicians should maintain awareness of this potential adverse effect.
Imaging approaches for pulmonary vein isolation in patients after lobectomy or pneumonectomy: a case series
Authors: Rahm Ann-Kathrin , Linz Dominik , Gang Uffe Jakob Ortved
Published: March 2023

Background

In patients who underwent pneumonectomy, pulmonary vein isolation for atrial fibrillation by catheter ablation may be complicated by the anatomical alterations caused by the surgical intervention. Pre- and peri-procedural imaging can visualize and guide the procedure to assure safety and procedural success.

Case summary

This case series describes different imaging and ablation strategies in three cases from three different ablation centres with the unusually challenging and complex anatomical conditions in patients following lobectomy or pneumonectomy.

Discussion

Pulmonary vein isolation in patients with previous pulmonary resection was feasible by both radiofrequency and cryocatheter ablation despite the anatomical alterations caused by the surgery. Pre- and peri-procedural imaging by cardiac computed tomography and transoesophageal echocardiography contributed to an increased understanding of the complex anatomical substrate.
Electrical isolation of the right ventricular outflow tract in idiopathic ventricular tachycardia: a case report
Authors: Popa Miruna A , Hessling Gabriele , Deisenhofer Isabel , Bourier Felix
Published: March 2023

Background

Ventricular tachycardia (VT) originating in the right ventricular outflow tract (RVOT) is the most common form of idiopathic VT. Catheter ablation of right ventricular outflow tract tachycardia (RVOT-VT) is associated with high success rates. However, non-inducibility of VT on electrophysiological (EP) study can severely impact ablation outcome. We describe a novel catheter ablation strategy which proved feasible and safe in a case of highly symptomatic, non-inducible RVOT-VT.

Case summary

A 51-year-old male with a history of non-sustained VT (NSVT) was referred to our hospital after two syncopal episodes resulting in collapse. Upon admission, a cluster of monomorphic NSVT (250–270 b.p.m.) resulted in haemodynamic instability and required transfer to the intensive care unit. On twelve-lead electrocardiogram, NSVT showed inferior axis and left bundle branch block, suggestive of RVOT-VT. Diagnostic workup including echocardiography, coronary angiography, and late enhancement computed tomography (CT) revealed no evidence of structural heart disease. On two EP studies, non-inducibility of clinical VT despite repeated ventricular pacing and isoproterenol infusion rendered precise mapping of triggered activity unfeasible. Therefore, a bailout ablation strategy was developed by performing a circumferential electrical RVOT isolation using a 3.5 mm irrigated-tip ablation catheter under the guidance of high-density electroanatomic mapping (CARTO® 3) and CT reconstruction of cardiac anatomy. No procedural complications occurred, and the patient remained arrhythmia-free during a 6-month follow-up period.

Discussion

Catheter ablation is a first-line therapy for symptomatic and drug-refractory idiopathic RVOT-VT. Non-inducibility of RVOT-VT represents a relevant limitation for successful ablation which might be overcome by electrical RVOT isolation as a bailout ablation strategy.
The impact of steerable sheath visualization during catheter ablation for atrial fibrillation
Authors: Fitzpatrick Noel , Mittal Ashish , Galvin Joseph , Jauvert Gael , Keaney John , Keelan Edward , O’Brien Jim , Széplaki Gábor
Published: March 2023

Aims

Incorporating a steerable sheath that can be visualized using an electroanatomical mapping (EAM) system may allow for more efficient mapping and catheter placement, while reducing radiation exposure, during ablation procedures for atrial fibrillation (AF). This study evaluated fluoroscopy usage and procedure times when a visualizable steerable sheath was used compared with a non-visualizable steerable sheath for catheter ablation for AF.

Methods and results

In this retrospective, observational, single-centre study, patients underwent catheter ablation for AF using a steerable sheath that is visualizable using the CARTO EAM (VIZIGO; n = 57) or a non-visualizable steerable sheath (n = 34). The acute procedural success rate was 100%, with no acute complications in either group. Use of the visualizable sheath vs. the non-visualizable sheath was associated with a significantly shorter fluoroscopy time [median (first quartile, third quartile), 3.4 (2.1, 5.4) vs. 5.8 (3.8, 8.6) min; P = 0.003], significantly lower fluoroscopy dose [10.0 (5.0, 20.0) vs. 18.5 (12.3, 34.0) mGy; P = 0.015], and significantly lower dose area product [93.0 (48.0, 197.9) vs. 182.2 (124.5, 355.0) μGy·m2; P = 0.017] but with a significantly longer mapping time [12.0 (9.0, 15.0) vs. 9.0 (7.0, 11.0) min; P = 0.004]. There was no significant difference between the visualizable and non-visualizable sheaths in skin-to-skin time [72.0 (60.0, 82.0) vs. 72.0 (55.5, 80.8) min; P = 0.623].

Conclusion

In this retrospective study, use of a visualizable steerable sheath for catheter ablation of AF significantly reduced radiation exposure vs. a non-visualizable steerable sheath. Although mapping time was longer with the visualizable sheath, the overall procedure time was not increased.
Discrimination between falls and blows from the localization and the number of fractures on computed tomography scans of the skull and the trunk
Authors: Henriques Mélanie , Saliba-Serre Bérengère , Martrille Laurent , Blum Alain , Chaumoître Kathia , Donato Paulo , Campos Nuno , Cunha Eugénia , Adalian Pascal
Published: March 2023

The distinction between falls and blows is a common and difficult task in forensic sciences. One of the most often used criteria to address this issue is the hat brim line (HBL) rule, which states that fall-related injuries do not lie above the HBL. Some studies, however, have found that the use of HBL rule is not so relevant. This study assesses the aetiologies, the number of fractures, and their location on the skull and the trunk in a sample of 400 individuals aged 20–49 years, which were CT scanned after traumas. This may facilitate the interpretation of such injuries in skeletonized or heavily decomposed bodies in which soft tissues are no longer available. Our aim is to improve the distinction rate between falls and blows by combining several criteria and assessing their predictability. Skeletal lesions were analysed using retrospective CT scans. Cases selected comprise 235 falls and 165 blows. We registered the presence and the number of fractures in 14 skeletal anatomical regions related to the two different aetiologies. We showed that the HBL rule should be used with caution, but there is nevertheless a possibility of discussing the aetiology of blunt fractures. Possibly, parameters like the anatomical location and the number of fractures by region can be used to distinguish falls and blows.
Whole-exome sequencing prioritizes candidate genes for hereditary cataract in the Emory mouse mutant
Authors: Bennett Thomas M , Zhou Yuefang , Meyer Kacie J , Anderson Michael G , Shiels Alan
Published: March 2023

The Emory cataract (Em) mouse mutant has long been proposed as an animal model for age-related or senile cataract in humans—a leading cause of visual impairment. However, the genetic defect(s) underlying the autosomal dominant Em phenotype remains elusive. Here, we confirmed development of the cataract phenotype in commercially available Em/J mice [but not ancestral Carworth Farms White (CFW) mice] at 6–8 months of age and undertook whole-exome sequencing of candidate genes for Em. Analysis of coding and splice-site variants did not identify any disease-causing/associated mutations in over 450 genes known to underlie inherited and age-related forms of cataract and other lens disorders in humans and mice, including genes for lens crystallins, membrane/cytoskeleton proteins, DNA/RNA-binding proteins, and those associated with syndromic/systemic forms of cataract. However, we identified three cataract/lens-associated genes each with one novel homozygous variant including predicted missense substitutions in Prx (p.R167C) and Adamts10 (p.P761L) and a disruptive in-frame deletion variant (predicted missense) in Abhd12 (p.L30_A32delinsS) that were absent in CFW and over 35 other mouse strains. In silico analysis predicted that the missense substitutions in Prx and Adamts10 were borderline neutral/damaging and neutral, respectively, at the protein function level, whereas, that in Abhd12 was functionally damaging. Both the human counterparts of Adamts10 and Abhd12 are clinically associated with syndromic forms of cataract known as Weil-Marchesani syndrome 1 and polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract syndrome, respectively. Overall, while we cannot exclude Prx and Adamts10, our data suggest that Abhd12 is a promising candidate gene for cataract in the Em/J mouse.
Division promotes adult stem cells to perform active niche competition
Authors: Zhang Qian , Zhang Yang , Zhang Qi , Li Le , Zhao Shaowei
Published: March 2023

Adult stem cells maintain homeostatic self-renewal through the strategy of either population or single-cell asymmetry, and the former type of stem cells are thought to take passive while the latter ones take active competition for niche occupancy. Although the division ability of stem cells is known to be crucial for their passive competition, whether it is also crucial for active competition is still elusive. Drosophila female germline stem cells are thought to take active competition, and bam mutant germ cells are more competitive than wild-type germline stem cells for niche occupancy. Here we report that either cycB, cycE, cdk2, or rheb null mutation drastically attenuates the division ability and niche occupancy capacity of bam mutant germ cells. Conversely, accelerating their cell cycle by mutating hpo has an enhanced effect. Last but not least, we also determine that E-cadherin, which was proposed to be crucial previously, just plays a mild role in bam mutant germline niche occupancy. Together with previous studies, we propose that division ability plays a unified crucial role in either active or passive competition among stem cells for niche occupancy.
The curse and blessing of abundance—the evolution of drug interaction databases and their impact on drug network analysis
Authors: Udrescu Mihai , Ardelean Sebastian Mihai , Udrescu Lucreţia
Published: March 2023

Background

Widespread bioinformatics applications such as drug repositioning or drug–drug interaction prediction rely on the recent advances in machine learning, complex network science, and comprehensive drug datasets comprising the latest research results in molecular biology, biochemistry, or pharmacology. The problem is that there is much uncertainty in these drug datasets—we know the drug–drug or drug–target interactions reported in the research papers, but we cannot know if the not reported interactions are absent or yet to be discovered. This uncertainty hampers the accuracy of such bioinformatics applications.

Results

We use complex network statistics tools and simulations of randomly inserted previously unaccounted interactions in drug–drug and drug–target interaction networks—built with data from DrugBank versions released over the plast decade—to investigate whether the abundance of new research data (included in the latest dataset versions) mitigates the uncertainty issue. Our results show that the drug–drug interaction networks built with the latest dataset versions become very dense and, therefore, almost impossible to analyze with conventional complex network methods. On the other hand, for the latest drug database versions, drug–target networks still include much uncertainty; however, the robustness of complex network analysis methods slightly improves.

Conclusions

Our big data analysis results pinpoint future research directions to improve the quality and practicality of drug databases for bioinformatics applications: benchmarking for drug–target interaction prediction and drug–drug interaction severity standardization.
Effectiveness of hierarchical medical system policy: an interrupted time series analysis of a pilot scheme in China
Authors: Hu Huajie , Wang Ruilin , Li Huangqianyu , Han Sheng , Shen Peng , Lin Hongbo , Guan Xiaodong , Shi Luwen
Published: March 2023

The Chinese healthcare system faces a dilemma between its hospital-centric approach to healthcare delivery and a rapidly ageing population that requires strong primary care. To improve system efficiency and continuity of care, the Hierarchical Medical System (HMS) policy package was issued in November 2014 and fully implemented in 2015 in Ningbo, Zhejiang province, China. This study aimed to investigate the impact of the HMS on the local healthcare system. We conducted a repeated cross-sectional study with quarterly data collected between 2010 and 2018 from Yinzhou district, Ningbo. The data were analysed with an interrupted time series design to assess the impact of HMS on the changes in levels and trends of three outcome variables: primary care physicians’ (PCPs’) patient encounter ratio (i.e. the mean quarterly number of patient encounters of PCPs divided by that of all other physicians), PCP degree ratio (i.e. the mean degree of PCPs divided by the mean degree of all other physicians, with the mean degree revealing the mean activity and popularity of physicians, which reflected the extent to which he/she coordinated with others in delivering health services), and PCP betweenness centrality ratio (i.e. the mean betweenness centrality of PCPs divided by the mean betweenness centrality of all other physicians; the mean betweenness centrality was interpreted as the mean relative importance of physicians within the network, indicating the centrality of the network). Observed results were compared with counterfactual scenarios computed based on pre-HMS trends. Between January 2010 and December 2018, 272 267 patients visited doctors for hypertension, a representative non-communicable disease with a high prevalence of 44.7% among adults aged 35–75 years, amounting to a total of 9 270 974 patient encounters. We analysed quarterly data of 45 464 observations over 36 time points. Compared to the counterfactual, by the fourth quarter of 2018, the PCP patient encounter ratio rose by 42.7% [95% confidence interval (CI): 27.1–58.2, P < 0.001], the PCP degree ratio increased by 23.6% (95%CI: 8.6–38.5, P < 0.01) and the PCP betweenness centrality ratio grew by 129.4% (95%CI: 87.1–171.7, P < 0.001). The HMS policy can incentivize patients to visit primary care facilities and enhance the centrality of PCPs within their professional network.
The role of community health advisors’ cancer history in implementation and efficacy of a cancer control intervention
Authors: Huq Maisha R , He Xin , Woodard Nathaniel , Chen Chang , Knott Cheryl L
Published: March 2023

Community health advisors (CHAs) play a key role in promoting health in medically underserved communities, including in addressing cancer disparities. There is a need to expand the research on what characteristics make for an effective CHA. We examined the relationship between CHA personal and family history of cancer, and implementation and efficacy outcomes in a cancer control intervention trial. Twenty-eight trained CHAs implemented a series of three cancer educational group workshops for N = 375 workshop participants across 14 churches. Implementation was operationalized as participant attendance at the educational workshops, and efficacy as workshop participants’ cancer knowledge scores at the 12-month follow-up, controlling for baseline scores. CHA personal history of cancer was not significantly associated with implementation, nor knowledge outcomes. However, CHAs with family history of cancer had significantly greater participant attendance at the workshops than CHAs without family history of cancer (P = 0.03) and a significant, positive association with male workshop participants’ prostate cancer knowledge scores at 12 months (estimated beta coefficient = 0.49, P < 0.01) after adjusting for confounders. Findings suggest that CHAs with family history of cancer may be particularly suitable for cancer peer education, although further research is needed to confirm this and identify other factors conducive to CHA success.
Standardizing fishery-dependent catch-rate information across gears and data collection programs for Alaska sablefish (Anoplopoma fimbria)
Authors: Cheng M L H , Rodgveller C J , Langan J A , Cunningham C J
Published: March 2023

Indices of abundance used to inform stock assessment models are commonly derived from fishery-dependent data sources. However, fishery catch-per-unit-effort (CPUE) are often confounded by a myriad of factors for which corrections must be made using model-based standardization methods. The Alaska sablefish (Anoplopoma fimbria) fishery provides a fitting case study of such issues, wherein a regulatory change in 2017 disrupted historic fishery dynamics, promoting a rapid transition in use of pot gear over demersal hook-and-line gear in the Gulf of Alaska. To address this, we combined across both observer and logbook programs (data sources) and gear types to develop an intercalibrated abundance index. We first regressed observer records against vessel logbooks to understand potential biases that may arise from combining data sources during the CPUE standardization process. Here, we found that both data sources exhibited strong agreement in reported CPUEs when compared on a set-by-set basis. Therefore, we intercalibrated both CPUE data sources and developed an index of abundance that incorporated catch records from both demersal hook-and-line and pot gear fisheries for sablefish in Alaska, to account for the recent rapid change in gear use. This standardized index of abundance compared favourably with an index generated from a fishery-independent hook-and-line survey currently used in management, suggesting it is representative of sablefish population trends. Our findings not only represent a valuable contribution to the management of sablefish in Alaska, but also provide a widely applicable framework for standardizing fishery-dependent CPUE data to support the management of multi-gear fisheries.
The Positive Tropical Grassmannian, the Hypersimplex, and them= 2 Amplituhedron
Authors: Łukowski Tomasz , Parisi Matteo , Williams Lauren K
Published: March 2023

The positive Grassmannian $Gr^{\geq 0}_{k,n}$ is a cell complex consisting of all points in the real Grassmannian whose Plücker coordinates are non-negative. In this paper we consider the image of the positive Grassmannian and its positroid cells under two different maps: the moment map$\mu $ onto the hypersimplex [ 31] and the amplituhedron map$\tilde{Z}$ onto the amplituhedron [ 6]. For either map, we define a positroid dissection to be a collection of images of positroid cells that are disjoint and cover a dense subset of the image. Positroid dissections of the hypersimplex are of interest because they include many matroid subdivisions; meanwhile, positroid dissections of the amplituhedron can be used to calculate the amplituhedron’s ‘volume’, which in turn computes scattering amplitudes in $\mathcal{N}=4$ super Yang-Mills. We define a map we call T-duality from cells of $Gr^{\geq 0}_{k+1,n}$ to cells of $Gr^{\geq 0}_{k,n}$ and conjecture that it induces a bijection from positroid dissections of the hypersimplex $\Delta _{k+1,n}$ to positroid dissections of the amplituhedron $\mathcal{A}_{n,k,2}$; we prove this conjecture for the (infinite) class of BCFW dissections. We note that T-duality is particularly striking because the hypersimplex is an $(n-1)$-dimensional polytope while the amplituhedron $\mathcal{A}_{n,k,2}$ is a $2k$-dimensional non-polytopal subset of the Grassmannian $Gr_{k,k+2}$. Moreover, we prove that the positive tropical Grassmannian is the secondary fan for the regular positroid subdivisions of the hypersimplex, and prove that a matroid polytope is a positroid polytope if and only if all 2D faces are positroid polytopes. Finally, toward the goal of generalizing T-duality for higher $m$, we define the momentum amplituhedron for any even $m$.