Characterisation of pulmonary air leak measurements using a mechanical ventilator in a bench setup.

Prolonged air leakage (AL) following pulmonary resections leads to prolonged hospital stay and post-operative complications. Intra- and postoperative quantification of AL might be useful for improving treatment decisions, but these measurements have not been characterised. AL calculations based on inspiratory and expiratory tidal volumes were investigated in an Intensive Care Unit mechanical ventilator circuit (Servo-I). AL was also measured by a digital chest drainage system. This study shows that AL measurements increase in accuracy when corrected for baseline deviations (R: 0.904 > 0.997, p < 0.001). Bland-Altman analysis revealed a funnel-shape, indicative of a detection threshhold. Corrected measurements were most accurate when averaged over five breaths and AL was >500 mL/min, with an estimated mean systemic bias of 7.4% (95%-limits of agreement [LoA]: 1.1%-13.7%) at 500 mL/min air leak. Breath-by-breath analysis showed most accurate results at AL >20 mL/breath (R: 0.989-0.991, p < 0.001) at tidal volumes between 350-600 mL. The digital drain had a mean systemic bias of -11.1% (95%-LoA: -18.9% to -3.3%) with homogenous scatter in Bland-Altman analysis and a strong correlation to the control measurement over a large range (0-2000mL/min, R: 0.999, p < 0.001). This study indicates that the Servo-I can be used for air leak quantification in clinically relevant ranges (>500 mL/min), but is unsuited for small leak detection due to a detection threshold. Researchers and clinicians should be aware of varying accuracy and interoperability characteristics between AL measurement devices.

Proof-of-principle of a lung sealant based on functionalized polyoxazolines: experiments in an ovine acute aerostasis model.

OBJECTIVES: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury. METHODS: An acute aerostasis model was used in healthy adult female sheep, involving bilateral thoracotomy, amputation lesions (bronchioles Ø > 1.5 mm), sealant application, digital chest tube for monitoring AL, spontaneous ventilation, obduction and bursting pressure measurement. Two experiments were performed: (i) 3 sheep with 2 lesions per lung (N = 4 NHS-POx double-layer, N = 4 NHS-POx single-layer, N = 4 untreated) and (ii) 3 with 1 lesion per lung (N = 3 NHS-POx single-layer, N = 3 untreated). In pooled linear regression, AL was analysed per lung (N = 7 NHS-POx, N = 5 untreated) and bursting pressure per lesion (N = 11 NHS-POx, N = 7 untreated). RESULTS: Baseline AL was similar between groups (mean 1.38-1.47 l/min, P = 0.90). NHS-POx achieved sealing in 1 attempt in 8/11 (72.7%) and in 10/11 (90.9%) in >1 attempt. Application failures were only observed on triangular lesions requiring 3 folds around the lung. No influences of methodological variation between experiments was detected in linear regression (P > 0.9). AL over initial 3 h of drainage was significantly reduced for NHS-POx [median: 7 ml/min, length of interquartile range: 333 ml/min] versus untreated lesions (367 ml/min, length of interquartile range: 680 ml/min, P = 0.036). Bursting pressure was higher for NHS-POx (mean: 33, SD: 16 cmH2O) versus untreated lesions (mean: 19, SD: 15 cmH2O, P = 0.081). CONCLUSIONS: NHS-POx was effective for reducing early AL, and a trend was seen for improvement of bursting strength of the covered defect. Results were affected by application characteristics and lesion geometry.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing. Methods: An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo, extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo. Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology. Results: Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo, lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes). Conclusions: Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants.

Handgrip exercise in patients scheduled for cardiac surgery to attenuate troponin release: a feasibility study.

Cardiac surgery, including surgical aortic valve repair (SAVR) and coronary artery bypass grafting (CABG), are associated with ischemia-reperfusion (I/R) injury. Single bouts of exercise, including handgrip exercise, may protect against I/R injury. This study explored 1) the feasibility of daily handgrip exercise in the week before SAVR and/or CABG and 2) its impact on cardiac I/R injury, measured as postoperative cardiac troponin-T (cTnT) release. Sixty-five patients undergoing elective SAVR and/or CABG were randomized to handgrip exercise + usual care (intervention, n = 33) or usual care alone (control, n = 32). Handgrip exercise consisted of daily 4 × 5-min handgrip exercise (30% maximal voluntary contraction) for 2-7 days before cardiac surgery. Feasibility was assessed using validated questionnaires. Postoperative cTnT release was assessed at 0, 6, 12, 18, and 24 h [primary outcome area under the curve (cTnTAUC)]. Most patients (93%) adhered to handgrip exercise and 77% was satisfied with this intervention. Handgrip exercise was associated with lower cTnTAUC (402,943 ± 225,206 vs. 473,300 ± 232,682 ng · min/L), which is suggestive of a medium effect size (Cohen's d 0.31), and lower cTnTpeak (313 [190-623] vs. 379 [254-699] ng/L) compared with controls. We found that preoperative handgrip exercise is safe and feasible for patients scheduled for SAVR and/or CABG and is associated with a medium effect size to reduce postoperative cardiac I/R injury. This warrants future studies to assess the potential clinical impact of exercise protocols before cardiac surgery.NEW & NOTEWORTHY Daily handgrip exercise in the week before elective cardiac surgery is safe and feasible. Handgrip exercise is associated with a medium effect size for less troponin-T release. Future larger-sized studies are warranted to explore the impact of (handgrip) exercise prior to cardiac surgery on clinical outcomes and direct patient benefits.

Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.

AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Sealing effectiveness of a novel NHS-POx based patch: experiments in a dynamic ex vivo porcine lung.

Background: Sealants are used to prevent prolonged pulmonary air leakage (PAL) after lung resections (incidence 5.6-30%). However, clinical evidence to support sealant use is insufficient, with an unmet need for a more effective product. We compared a novel gelatin patch impregnated with functionalized polyoxazolines (NHS-POx) (GATT-Patch) to commercially available sealant products. Methods: GATT-Patch Single/Double layers were compared to Progel®, Coseal®, Hemopatch® and TachoSil® in an ex vivo porcine lung model (first experiment). Based on these results, a second head-to-head comparison between GATT-Patch Single and Hemopatch® was performed. Air leakage (AL) was assessed in three settings using increasing ventilatory pressures (max =70 cmH2O): (I) baseline, (II) with 25 mm × 25 mm superficial pleural defect, and (III) after sealant application. Lungs floating on saline (37 ℃) were video recorded for visual AL assessment. Pressure and tidal volumes were collected from the ventilator, and bursting pressure (BP), AL and AL-reduction were determined. Results: Per sealant 10 measurements were performed (both experiments). In the first experiment, BP was superior for GATT-Patch Double (60±24 cmH2O) compared to TachoSil® (30±11 cmH2O, P<0.001), Hemopatch® (33±6 cmH2O, P=0.006), Coseal® (25±13 cmH2O, P=0.001) and Progel® (33±11 cmH2O, P=0.005). AL-reduction was superior for GATT-Patch Double (100%±1%) compared to Hemopatch® (46%±50%, P=0.010) and TachoSil® (31%±29%, P<0.001), and also for GATT-Patch Single (100%±14%, P=0.004) and Progel (89%±40%, P=0.027) compared to TachoSil®. In the second experiment, GATT-Patch Single was superior regarding BP (45±10 vs. 40±6 cmH2O, P=0.043) and AL-reduction (100%±11% vs. 68%±40%, P=0.043) when compared to Hemopatch®. Conclusions: The novel NHS-POx patch shows promise as a lung sealant, demonstrating elevated BP, good adhesive strength and a superior AL-reduction.

Contamination of selected heavy metals in Limnothrissa miodon (Boulenger, 1906) in the four strata of Lake Kariba Zambia: are the consumers at risk?

Pollution of aquatic ecosystems is one of the major challenges affecting many countries of the world. Heavy metal pollutants, in particular, threaten the life of aquatic organisms (fauna and flora) and, more importantly, humans who consume aquatic products as a critical source of proteins. In the present study, the concentrations of selected heavy metals (cobalt- Co, Chromium-Cr, nickel- Ni and manganese- Mn) in Limnothrissa miodon, locally known as 'Kapenta' were assessed using the Microwave Plasma Atomic Emission Spectrometer (MP AES) 4200 at the Zambia Agricultural Research Institute (ZARI). The fish was collected from Lake Kariba, Zambia, which is divided into four fisheries management strata (I, II, III, and IV). The health risks to consumers were evaluated using the Estimated Daily Intake (EDI), Target Hazard Quotient (THQ) and Hazard Index (HI). Analysis of variance (ANOVA) was used to assess the difference in the means of heavy metal concentration across the four strata for each element. The concentrations of all the heavy metal elements were within the permissible limits considered to be safe for human consumption based on the Food and Agriculture Organization (FAO) standards. However, the concentration of individual heavy metal elements varied significantly across the strata with stratum I and II showing higher levels in general except for Mn which was highest in stratum II and III compared with the other strata. Furthermore, Mn concentration was the highest in all the strata and the highest concentration was observed in the fish from stratum II. The EDIs, THQs and HIs of each heavy metal element did not show any threat to consumers of the fish from the lake. Further studies are required to better understand the potential sources of heavy metals and to regularly monitor existing activities that may elevate the concentration levels.

Prevalence of Low-Frequency, Antiviral Resistance Variants in SARS-CoV-2 Isolates in Ontario, Canada, 2020-2023.

Importance: Nirmatrelvir-ritonavir is an oral antiviral medication that improves outcomes in SARS-CoV-2 infections. However, there is concern that antiviral resistance will develop and that these viruses could be selected for after treatment. Objective: To determine the prevalence of low-frequency SARS-CoV-2 variants in patient samples that could be selected for by nirmatrelvir-ritonavir. Design, Setting, and Participants: This retrospective cohort study was conducted at 4 laboratories that serve community hospitals, academic tertiary care centers, and COVID-19 assessment centers in Ontario, Canada. Participants included symptomatic or asymptomatic patients who tested positive for SARS-CoV-2 virus and submitted virus samples for diagnostic testing between March 2020 and January 2023. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Samples with sufficient viral load underwent next-generation genome sequencing to identify low-frequency antiviral resistance variants that could not be identified through conventional sequencing. Results: This study included 78 866 clinical samples with next-generation whole-genome sequencing data for SARS-CoV-2. Low-frequency variants in the viral nsp5 gene were identified in 128 isolates (0.16%), and no single variant associated with antiviral resistance was predominate. Conclusions and Relevance: This cohort study of low-frequency variants resistant to nirmatrelvir-ritonavir found that these variants were very rare in samples from patients with SARS-CoV-2, suggesting that selection of these variants by nirmatrelvir-ritonavir following the initiation of treatment may also be rare. Surveillance efforts that involve sequencing of viral isolates should continue to monitor for novel resistance variants as nirmatrelvir-ritonavir is used more broadly.

Evaluating and developing sealants for the prevention of pulmonary air leakage: A systematic review of animal models.

Sealants may provide a solution for pulmonary air leakage (PAL), but their clinical application is debatable. For sealant comparison, standardized animal models are lacking. This systematic review aims to assess methodology and quality of animal models for PAL and sealant evaluation. All animal models investigating lung sealing devices (e.g., staplers, glues, energy devices) to prevent or treat PAL were retrieved systematically from Embase, Pubmed and Web of science. Methodological study characteristics, risk of bias, reporting quality and publication bias were assessed. A total of 71 studies were included (N = 75 experiments, N = 1659 animals). Six different species and 18 strains were described; 92% of experiments used healthy animals, disease models were used in only six studies. Lesions to produce PAL were heterogenous, and only 11 studies used a previously reported technique, encompassing N = 5 unique lesions. Clinically relevant outcomes were used in the minority of studies (imaging 16%, air leak 10.7%, air leak duration 4%). Reporting quality was poor, but revealed an upward trend per decade. Overall, high risk of bias was present, and only 18.7% used a negative control group. All but one study without control groups claimed positive outcomes (95.8%), in contrast to 84.3% using positive or negative control groups, which also concluded equivocal, adverse or inconclusive outcomes. In conclusion, animal studies evaluating sealants for prevention of PAL are heterogenous and of poor reporting quality. Using negative control groups, disease models and quantifiable outcomes seem important to increase validity and relevance. Further research is needed to reach consensus for model development and standardization.

High-quality read-based phasing of cystic fibrosis cohort informs genetic understanding of disease modification.

Phasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of CFTR haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a PRSS2 missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are PRSS2 pancreas eQTLs (p = 9.5 × 10-7 and p = 1.4 × 10-4, respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute.

Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder.

Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We develop a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD have a significantly higher GRVS compared to those with nondysmorphic ASD (P = 0.03). Using the polygenic transmission disequilibrium test, we observe an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P = 2.9 × 10-3). These findings replicate using WGS data from 442 ASD probands with accompanying morphology data from the Simons Simplex Collection. Our results provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.

Long-term follow-up of voice changes after cervical mediastinoscopy.

BACKGROUND: Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up. METHODS: A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes. RESULTS: Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%. CONCLUSIONS: Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.

Timing of cardiac surgery during pregnancy: a patient-level meta-analysis.

AIMS: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes. METHODS AND RESULTS: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality. CONCLUSION: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.

Anatomical analysis of variations in the bronchus pattern of the left upper lobe using three-dimensional computed tomography angiography and bronchography.

Background: The number of sublobar resections performed is increasing, thoracic surgeons must be familiar with bronchus anatomy and preoperative planning plays an important role in predicting anatomical variations. However, there is few report showing anatomic variations of the left upper lobe (LUL) using three-dimensional computed tomography angiography and bronchography (3D-CTAB), and no in Chinese population. The present study aimed to use 3D-CTAB to describe variations of the pulmonary bronchus of LUL in Chinese population. Methods: In this retrospective study, we analyzed 3D-reconstruction from patients that performed lobectomy, segmentectomy or subsegmentectomy of the LUL in 2020 at Fujian Medical University Cancer Hospital's Department of Thoracic Surgery. Patients with previous LUL surgery or absence of 3D-reconstruction or without surgery were excluded. Results: One hundred and sixty-six patients met our criteria. Branching of the left upper bronchus was classified into bifurcated type (99.4%) or trifurcated type (0.06%). The left upper divisional bronchus (B 1+2+3) arise as bifurcated (65.65%) or trifurcated type (34.34%). Apicodorsalis bronchus (B 1+2) always originated as bifurcated type, while ventralis bronchus (B 3) was either bifurcated (94.45%) or trifurcated (5.55%). Lingular bronchus (B 4+5) was observed as bifurcated (96.38%) or trifurcated (3.62%) type. When analyzing sublobar divisions of bronchi a total of 14 subtypes were identified, 6 of them were found in the upper divisional bronchus. Conclusions: Bronchial anatomy of LUL is highly variable, especially in upper divisional bronchus. 3D-CTAB is a useful tool to identify variations in the bronchi pattern, we recommend preoperative planning for sublobar resection.

Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy.

Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10-7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7-58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.

Breeding pattern of Oreochromis niloticus (Linnaeus, 1758) versus native congeneric species, Oreochromis macrochir (Boulinger, 1912), in the upper Kabompo River, northwest of Zambia.

Investigating the determinants of the reproductive biology of fishes is an essential component of fisheries research. Tilapia breeding patterns were investigated to determine the impact of non-native Oreochromis niloticus on the native congeneric Oreochromis macrochir in the upper Kabompo River in the Northwest of Zambia using the gonadosomatic index and the sex ratios. Oreochromis niloticus was the most abundant fish caught (221, 63.5%) than O. macrochir (127, 36.5%). Results showed that the overall gonadosomatic index means of O. macrochir in both sections were similar. Oreochromis macrochir bred in December and February-March, with no reproduction in June. However, O. niloticus in the invaded section indicated all year reproduction through reduced spawning in May-June, with increased spawning activity in February-March. The sex ratio (females: males) was 1:1.3 and 1:1.7 for O. niloticus and O. macrochir, respectively, and both significantly deviated from the sex ratio of 1:1 (ꭓ2 = 8.42 and 9.37, p < .05). Our study has revealed that O. niloticus was able to spawn across all sampled months with a 23% higher breeding population than O. macrochir, which might explain the suppression in the abundance of native O. macrochir. Due to the superior breeding patterns of O. niloticus, fisheries, wildlife, and aquaculture practitioners need to make contingency plans to alleviate its impacts further downstream of the Kabompo River.