bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic vessel injuries initiating hemostasis generate high shear conditions
Authors: Yakusheva Alexandra A. , Butov Kirill R. , Bykov Georgii A. , Závodszky Gábor , Eckly Anita , Ataullakhanov Fazly I. , Gachet Christian , Panteleev Mikhail A. , Mangin Pierre H.
Published: June 2022

Blood flow is a major regulator of hemostasis and arterial thrombosis. The current view is that low and intermediate flows occur in intact healthy vessels, whereas high shear levels (>2000 s−1) are reached in stenosed arteries, notably during thrombosis. To date, the shear rates occurring at the edge of a lesion in an otherwise healthy vessel are nevertheless unknown. The aim of this work was to measure the shear rates prevailing in wounds in a context relevant to hemostasis. Three models of vessel puncture and transection were developed and characterized for a study that was implemented in mice and humans. Doppler probe measurements supplemented by a computational model revealed that shear rates at the edge of a wound reached high values, with medians of 22 000 s−1, 25 000 s−1, and 7000 s−1 after puncture of the murine carotid artery, aorta, or saphenous vein, respectively. Similar shear levels were observed after transection of the mouse spermatic artery. These results were confirmed in a human venous puncture model, where shear rates in a catheter implanted in the cubital vein reached 2000 to 27 000 s−1. In all models, the high shear conditions were accompanied by elevated levels of elongational flow exceeding 1000 s−1. In the puncture model, the shear rates decreased steeply with increasing injury size. This phenomenon could be explained by the low hydrodynamic resistance of the injuries as compared with that of the downstream vessel network. These findings show that high shear rates (>3000 s−1) are relevant to hemostasis and not exclusive to arterial thrombosis.
RResolver: efficient short-read repeat resolution within ABySS
Authors: Nikolić Vladimir , Afshinfard Amirhossein , Chu Justin , Wong Johnathan , Coombe Lauren , Nip Ka Ming , Warren René L. , Birol Inanç
Published: June 2022

Background

De novo genome assembly is essential to modern genomics studies. As it is not biased by a reference, it is also a useful method for studying genomes with high variation, such as cancer genomes. De novo short-read assemblers commonly use de Bruijn graphs, where nodes are sequences of equal length k, also known as k-mers. Edges in this graph are established between nodes that overlap by $$k - 1$$

k
-
1

bases, and nodes along unambiguous walks in the graph are subsequently merged. The selection of k is influenced by multiple factors, and optimizing this value results in a trade-off between graph connectivity and sequence contiguity. Ideally, multiple k sizes should be used, so lower values can provide good connectivity in lesser covered regions and higher values can increase contiguity in well-covered regions. However, current approaches that use multiple k values do not address the scalability issues inherent to the assembly of large genomes.

Results

Here we present RResolver, a scalable algorithm that takes a short-read de Bruijn graph assembly with a starting k as input and uses a k value closer to that of the read length to resolve repeats. RResolver builds a Bloom filter of sequencing reads which is used to evaluate the assembly graph path support at branching points and removes paths with insufficient support. RResolver runs efficiently, taking only 26 min on average for an ABySS human assembly with 48 threads and 60 GiB memory. Across all experiments, compared to a baseline assembly, RResolver improves scaffold contiguity (NGA50) by up to 15% and reduces misassemblies by up to 12%.

Conclusions

RResolver adds a missing component to scalable de Bruijn graph genome assembly. By improving the initial and fundamental graph traversal outcome, all downstream ABySS algorithms greatly benefit by working with a more accurate and less complex representation of the genome. The RResolver code is integrated into ABySS and is available at https://github.com/bcgsc/abyss/tree/master/RResolver.
Diet evolution of carnivorous and herbivorous mammals in Laurasiatheria
Authors: Wu Yonghua
Published: June 2022

Background

Laurasiatheria contains taxa with diverse diets, while the molecular basis and evolutionary history underlying their dietary diversification are less clear.

Results

In this study, we used the recently developed molecular phyloecological approach to examine the adaptive evolution of digestive system-related genes across both carnivorous and herbivorous mammals within Laurasiatheria. Our results show an intensified selection of fat and/or protein utilization across all examined carnivorous lineages, which is consistent with their high-protein and high-fat diets. Intriguingly, for herbivorous lineages (ungulates), which have a high-carbohydrate diet, they show a similar selection pattern as that of carnivorous lineages. Our results suggest that for the ungulates, which have a specialized digestive system, the selection intensity of their digestive system-related genes does not necessarily reflect loads of the nutrient components in their diets but appears to be positively related to the loads of the nutrient components that are capable of being directly utilized by the herbivores themselves. Based on these findings, we reconstructed the dietary evolution within Laurasiatheria, and our results reveal the dominant carnivory during the early diversification of Laurasiatheria. In particular, our results suggest that the ancestral bats and the common ancestor of ruminants and cetaceans may be carnivorous as well. We also found evidence of the convergent evolution of one fat utilization-related gene, APOB, across carnivorous taxa.

Conclusions

Our molecular phyloecological results suggest that digestive system-related genes can be used to determine the molecular basis of diet differentiations and to reconstruct ancestral diets.
The mite Acarus farris inducing defensive behaviors and reducing fitness of termite Coptotermes formosanus: implications for phoresy as a precursor to parasitism
Authors: Chen Yong , Zhang Lijun , Zhang Shijun , Liu Bingrong , Zeng Wenhui , Li Zhiqiang
Published: June 2022

Background

The ecology and evolution of phoretic mites and termites have not been well studied. In particular, it is unknown whether the specific relationship between mites and termites is commensal or parasitic. High phoretic mite densities have often been found to occur in weak termite colonies, suggesting that the relationship is closer to that of parasitism than commensalism.

Results

To examine this,Coptotermes formosanuswas used as a carrier, andAcarus farrisas the phoretic mite. We used video recordings to observe termite social immunity behaviors and bioassay to examine termite fitness. Our results showed that the attachment of the mite on the termite can enhance termite social immunity behaviors like alarm vibration and grooming frequency while decreasing the duration of individual grooming episodes in phoretic mites. Further,A. farrisphoresy led to a 22.91% reduction in termite abdomen volume and a 3.31-fold increase in termite mortality.

Conclusions

When termites groom more frequently, the consequence is short duration of grooming bouts. This may be indicative of a trade-off which provides suggestive evidence that frequent social behaviors may cost termites energy. And this caused phoretic behavior hastened termites’ death, and helped propagate the population of mites feeding on dead termites. So, it provides a case for phoresy being a precursor to parasitism, and the specific relationship betweenA. farrisandC. formosanusis closer to parasitism than to commensalism.
Transcriptome study digs out BMP2 involved in adipogenesis in sheep tails
Authors: Jin Meilin , Fei Xiaojuan , Li Taotao , Lu Zengkui , Chu Mingxing , Di Ran , He Xiaoyun , Wang Xiangyu , Wei Caihong
Published: June 2022

Background

Hu sheep and Tibetan sheep in China are characterized by fat tails and thin tails, respectively. Several transcriptomes have been conducted in different sheep breeds to identify the differentially expressed genes (DEGs) underlying this trait. However, these studies identified different DEGs in different sheep breeds.

Results

Hence, RNA sequencing was performed on Hu sheep and Tibetan sheep. We obtained a total of 45.57 and 43.82 million sequencing reads, respectively. Two libraries mapped reads from 36.93 and 38.55 million reads after alignment to the reference sequences. 2108 DEGs were identified, including 1247 downregulated and 861 upregulated DEGs. GO and KEGG analyses of all DEGs demonstrated that pathways were enriched in the regulation of lipolysis in adipocytes and terms related to the chemokine signalling pathway, lysosomes, and glycosaminoglycan degradation. Eight genes were selected for validation by RT–qPCR. In addition, the transfection of BMP2 overexpression into preadipocytes resulted in increased PPAR-γ expression and expression. BMP2 potentially induces adipogenesis through LOX in preadipocytes. The number of lipid drops in BMP2 overexpression detected by oil red O staining was also greater than that in the negative control.

Conclusion

In summary, these results showed that significant genes (BMP2, HOXA11, PPP1CC and LPIN1) are involved in the regulation of adipogenesis metabolism and suggested novel insights into metabolic molecules in sheep fat tails.
The GALNS p.P77R variant is a probable Gujarati-Indian founder mutation causing Mucopolysaccharidosis IVA syndrome
Authors: Sheth Harsh , Naik Premal , Shah Maulin , Bhavsar Riddhi , Nair Aadhira , Sheth Frenny , Sheth Jayesh
Published: June 2022

Background

Mucopolysaccharidosis IVA (Morquio syndrome A, MPS IVA) is an autosomal recessive lysosomal storage disorder caused due to biallelic variants in the N-acetylgalactoseamine-6-sulfate sulfatase (GALNS) gene. The mutation spectrum in this condition is determined amongst sub-populations belonging to the north, south and east India geography, however, sub-populations of west Indian origin, especially Gujarati-Indians, are yet to be studied. We aimed to analyse the variants present in the GLANS gene amongst the population of Gujarat by sequencing all exons and exon–intron boundaries of the GALNS gene in patients from 23 unrelated families.

Results

We report 11 variants that include eight missense variants: (p.L36R, p.D39G, p.P77R, p.C79R, pP125L, p.P151L, p.G255A and p.L350P), one splice site variant: (c.121-7C > G), one small insertion: (c.1241_1242insA, p.I416HfsTer2) and one small deletion: (c.839_841delACA). Of these, three missense variants (p.D39G, p.G255A and p.L350P), one splice site and the two indels mentioned above are novel. Interestingly, we observed a higher than anticipated prevalence of p.P77R variant in our cohort (n = 14/25, 56%). Haplotype analysis in cases with p.P77R variant and 63 ethnicity matched healthy population controls suggested a 4 SNP haplotype block present in cases compared to controls (likelihood ratio test p-value = 1.16 × 10–13), thereby suggesting p.P77R variant as a founder variant in the Gujarati-Indian population. Furthermore, age of mutation analysis suggested the variant to have arisen approximately 450 years ago in the population.

Conclusion

p.P77R variant in the GLANS gene is likely to be a founder variant in MPS IVA patients of Gujarati-Indian ancestry and appeared approximately 450 years ago in the population. To our knowledge, this is the first variant to be posited as a founder variant in the GLANS gene in patients with MPS IVA syndrome.
Effect of spontaneous breathing trial on extubation in patients with acute exacerbation of chronic obstructive pulmonary disease under mechanical ventilation
Authors: Liu Wenjing , Guo Hong , Wang Jing , Ding Fang
Published: June 2022

Objective

To evaluate how spontaneous breathing trial (SBT) affects successful extubation and prognosis in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients under mechanical ventilation.

Methods

AECOPD patients under invasive mechanical ventilation were recruited into the study and divided into the SBT and non-SBT groups. SBT patients received SBT for 60 min before extubation, while non-SBT patients that met weaning criteria were immediately extubated without SBT.

Results

A total of 64 patients were enrolled in analysis, including 32 in SBT group and 32 in non-SBT group. Patients in the two groups had similar baseline demographics and clinical characteristics (all parameters: p =  > 0.05). Four (12.5%) patients in the SBT group and 5 (15.6%) in the non-SBT group were reintubated in 48 h of extubation (p = 0.821). During the 28-day follow-up after extubation, 3 patients died, 1 (3.1%) in the SBT group and 2 (6.3%) in the non-SBT group (p = 0.554).

Conclusion

Our findings indicate that SBT did not affect extubation success, in-hospital mortality, and 28-day survival in AECOPD patients under mechanical ventilation.
Clinico-pathological characteristics of obstructing colorectal cancer and its management outcomes at a tertiary referral center of Eastern Nepal
Authors: Kumar Abhijeet , Dhungana Sajan Babu , Gupta Rakesh Kumar , Sah Suresh Prasad , khanal Bhawani
Published: June 2022

Background

The aim of this study is to explore the treatment strategies being followed for patients with obstructing colorectal cancer (OCRC) at our institute and to know the management outcomes.

Methods

This study included 28 patients who were diagnosed with obstructing colorectal cancer (OCRC) either preoperatively or intraoperatively over a period of 5 years.

Results

Most were in the younger age group with mean age of 49.78 ± 15.96 years with 1/4th of the patients being younger than 40. There was no difference in incidence of OCRC among genders. It was found to be common in rural areas of the eastern Nepal, 16(57%) patients from such areas. 21.4% patients had complete bowel obstruction at presentation. The investigating modalities used were abdominal X-ray, ultrasonoghraphy of abdomen/pelvis, abdominal CT-scan, colonoscopy, serum CEA, punch biopsy and Faecal occult blood test. The anatomical shift to the right was observed with 54% lesions in the proximal colon. Majority were in advanced stage (stage 3:53.6%, stage 4:32.1%) with histologically adenocarcinoma (100%) and a higher incidence of synchronous lesion (28.6%). Patients averaged 13.82 days in the hospital with post-operative mortality rate of 3.6%. The 1-year and 2-years disease free survivals were 89.3% and 82.1% while overall survivals were 92.8% and 82.1% respectively.

Conclusion

In developing countries like ours, relatively younger patients present to health center with obstructive colorectal cancer with anatomical shift to the right sided lesions. The treatments provided at our center and their outcomes are not inferior to that of the developed world.
A randomised control trial protocol of MuST for vascular access cannulation in hemodialysis patients (MuST Study): contributions for a safe nursing intervention
Authors: Peralta Ricardo , Wammi Anna , Stauss-Gabo Manuela , Dias Óscar , Carvalho Helena , Cristóvão António
Published: June 2022

Background

The vascular access preservation and the maintenance of a complication-free fistula remains an Achilles’ heel of hemodialysis in chronic kidney patients due to its substantial contribution to the morbidity and mortality. Systematic studies in the area of examining cannulation practices, achieving complication-free cannulation, and strategies to improve fistula survival are needed. For this reason, we consider it essential to create and investigate new methodologies for approaching fistula in patients on regular HD.

The Multiple Single Cannulation Technique (MuST) is based on the association between the rope-ladder (RL) using the arteriovenous vessel through progressive rotation, and the buttonhole (BH) since there are three specific cannulation sites for each cannulation day during the week. The MuST is simple to implement and seems to be a very promising technique in terms of patient safety. Previous studies already showed an arteriovenous fistula survival similar to RL but significantly higher than BH.

Methods

This MuST study is a multicenter, prospective, non-blind, parallel-group, randomized controlled trial with the intervention group submitted to MuST and a control group undergoing the rope-ladder, up to 100 subjects for each group. Patients will be randomized 1:1 to one of two cannulation technique (CT), and the follow-up period of this study will be 12 months. Primary outcome is to evaluate the arteriovenous fistula survival rate at 12 months determined by the percentage of fistulas in use from the beginning of the study to the date of the first clinical intervention by angioplasty or vascular surgery, to maintain or restore patency (unassisted patency). Secondary outcome is to evaluate arteriovenous fistula survival rate at 12 month determined by the percentage of fistulas in use from the study start to the date of access abandonment due to dysfunction, patient abandonment, or death, treatment change modality or study end. We will also evaluate the assisted primary patency and include the following secondary outcomes associated with the cannulation technique: Infection, Hematoma, Aneurysm development, and pain.

Discussion

The study will investigate whether fistula survival can be improved when using cannulation by MuST compared to the RL. MuST study will provide important information on fistula survival when cannulated by MuST but also information related to its use in fistulas previously cannulated by other CTs.

Trial registration

ClinicalTrials.gov identifier NCT05081648 registered on 18 October 2021.
Influences of different referral modes on clinical outcomes after endovascular therapy for acute ischemic stroke
Authors: Hou Jie , Guo Zhi-liang , Huang Zhi-chao , Wang Huai-shun , You Shou-jiang , Xiao Guo-dong
Published: June 2022

Background and purpose

As endovascular thrombectomy (EVT) is time-dependent, it is crucial to refer patients promptly. Current referral modes include Mothership (MS), Drip and Ship (DS) and Drive the Doctor (DD). The purpose of this study was to investigate the influences of different referral modes on the clinical outcomes of patients with acute ischemic stroke after EVT. 

Methods

A total of 349 patients from 15 hospitals between April 2017 and March 2020 were enrolled. The primary outcomes include poor outcome (modified Rankin Scale score of 3 to 6), symptomatic intracranial hemorrhage transformation (sICH), mortality and cost. Regression analysis was used to assess the association of referral modes with poor outcome, sICH, mortality and cost in acute ischemic stroke patients.

Results

Among the 349 patients, 83 were in DD group (23.78%), 85 in MS group (24.36%) and 181 in DS group (51.86%). There were statistically significant differences in intravenous thrombolysis, onset-to-door time, onset-to-puncture time, puncture-to-recanalization time, door-to-puncture time, door-to-recanalization time, and cost among the DD, MS, and DS groups (59.04% vs 35.29% vs 33.15%, P<0.001; 90 vs 166 vs 170 minutes, P<0.001; 230 vs 270 vs 270 minutes, P<0.001; 82 vs 54 vs 51 minutes, P<0.001; 110 vs 85 vs 96 minutes, P=0.004; 210 vs 146 vs 150 minutes, P<0.001; 64258 vs 80041 vs 70750 Chinese Yuan, P=0.018). In terms of sICH, mortality and poor outcome, there was no significant difference among the DD, MS, and DS groups (22.89% vs 18.82% vs 19.34%, P=0.758; 24.10% vs 24.71% vs 29.83%, P=0.521; 64.47% vs 64.71% vs 68.51%, P=0.827). The results of multiple regression analysis indicated that there was no independent correlation between different referral modes regarding sICH (ORMS: 0.50, 95%CI: 0.18, 1.38, P=0.1830; ORDS: 0.47, 95%CI: 0.19, 1.16, P=0.1000), mortality (ORMS: 0.56, 95%CI: 0.19, 1.67, P=0.2993; ORDS: 0.65, 95%CI: 0.25, 1.69, P=0.3744) and poor outcome (ORMS: 0.61, 95%CI: 0.25, 1.47, P=0.2705; ORDS: 0.53, 95%CI: 0.24, 1.18, P=0.1223). However, there was a correlation between MS group and cost (β=30449.73, 95%CI: 11022.18, 49877.29; P=0.0023). The multiple regression analysis on patients finally admitted in comprehensive stroke center (MS+DS) versus patients finally admitted in primary stroke center (DD) showed that DD mode was independently associated with lower costs (β=-19438.86, 95%CI: -35977.79, -2899.94; P=0.0219).

Conclusion

There was no independent correlation between three referral modes and sICH, mortality, poor outcome correspondingly. Different referral modes can be implemented in clinical practice according to the situations encountered. Compared to MS and DS modes, DD mode is more economical.
“Incidence, characteristics and prognosis of cervical artery dissection-induced ischemic stroke in central Iran”
Authors: Ranjbar Mahta , Badihian Negin , Yazdi Maryam , Milani Shahaboddin , Taheri Marzieh , Khorvash Fariborz , Saadatnia Mohammad
Published: June 2022

Objectives

Ischemic stroke is the most common presentation of cervical artery dissection (CAD). Information regarding CAD-induced stroke is scarce, especially in the Middle East. Here we investigated the incidence of CAD-induced stroke, its characteristics, and the clinical course in central Iran.

Methods

This is an observational study conducted in the city of Isfahan, Iran. We recruited patients with ischemic stroke during 2017–2019. We analyzed characteristics of the CAD-induced stroke patients with regards to the involved vessel (internal carotid artery dissection (ICAD) or vertebral artery dissection (VAD)). We assessed functional outcome (modified Rankin Scale [mRS]) and recanalization status after 1 year of follow-up.

Results

Among 3630 ischemic stroke patients, 51(1.4%) had CAD-induced stroke (mean age: 41.8 ± 12.6; 40.4% female; 28 and 19 ICAD and VAD cases, respectively). The crude incidence rate of CAD-induced stroke was 1.20/100,000/year (0.66/100,000/year and 0.45/100,000/year for strokes due to ICAD and VAD, respectively). mRS ≤ 2 was present in 63.8% of the patients after 1 year of follow-up. History of exercise during the last days before stroke occurrence was associated with a better follow-up mRS (β = -3.1, p-value: 0.037). Administration of anticoagulant or double-antiplatelets was related neither to mRS nor recanalization results. Trauma (27.7%), smoking (21.3%), and headache disorders/migraine (21.3%) were the most common reported factors.

Conclusion

We found a crude incidence rate of 1.20/100,000/year for CAD-induced stroke. Trauma, smoking, and headache disorders were the most common reported factors among our patients. CAD-induced stroke had a favorable long-term prognosis regardless of the type of the involved vessel or the used medication.
Loneliness and coping skill mediate the association between child maltreatment and depression for rural males and females
Authors: Wang Meiqi , Xu Meixia , Sun Long
Published: June 2022

Background

Child maltreatment is a prevalent and notable problem in rural China, and the prevalence and severity of depression in rural areas are higher than the national norm. Several studies have found that loneliness and coping skills respectively mediated the relationship between child maltreatment and depression. However, few studies have examined the roles of loneliness and coping skills in child maltreatment and depression based on gender differences.

Methods

All participants were from rural communities aged more than 18 years in Shandong province, and 879 valid samples (female:63.4%) ranging in age from 18 to 91 years old were analyzed. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Center for Epidemiologic Studies-Depression (CES-D), the Simple Coping Style Questionnaire (SCSQ), and the Emotional and Social Loneliness Scale (ESLS) were used to evaluate child maltreatment, depression, coping skills and loneliness.

Results

Child maltreatment was more common and severe in males than females (F = 3.99; p < 0.05). Loneliness and coping skills partially mediated the relationship between child maltreatment and depression in males, but loneliness fully mediated the relationship between child maltreatment and depression in females.

Conclusion

In this study, males were more likely to experience child maltreatment. Child maltreatment and depression were correlated. We also found a mediating role of loneliness and coping skills for males and a mediating role of loneliness in females.
Catechol-O-methyltransferase activity in individuals with substance use disorders: a case control study
Authors: da Costa Azevedo Jacinto Nuno , Carvalho Cláudia , Serrão Maria Paula , Coelho Rui , Figueiredo-Braga Margarida , Vieira-Coelho Maria Augusta
Published: June 2022

Background

Impulsivity and substance use disorders (SUD) have been both associated with changes in dopaminergic processes. In this study, we intended to evaluate the dopaminergic function in imprisoned SUD offenders through the determination of s-COMT activity.

Methods

The study included 46 male individuals from a Portuguese penal institution. The participants were assessed through a battery of standardised instruments: Psychopathy Checklist-Revised (PCL-R), Barratt Impulsivity Scale Version 11 (BIS-11), and the European version of the Addiction Severity Index (EuropASI). In addition, s-COMT erythrocyte activity was evaluated.

Results

Overall, 73.9% (n = 34) of the individuals had Antisocial personality disorder (ASPD) and 58.7% (n = 27) presented SUD. We evidenced, for the first time, that, in individuals with SUD, s-COMT activity was correlated with the severity of drug dependence (EuropASI) (p = 0.009), and with BIS-11 factors self-control (p < 0.0001) and non-planning (p = 0.002).

Conclusions

This study opens new perspectives regarding the pharmacological intervention on substance dependence through the interference on dopamine pathways.
Young men are at higher risk of failure after ACL hamstring reconstructions: a retrospective multivariate analysis
Authors: Keuning Martine C. , Robben Bart J. , Brouwer Reinoud W. , Stevens Martin , Bulstra Sjoerd K. , Zuurmond Rutger G.
Published: June 2022

Background

Results of ACL reconstruction are influenced by both patient and surgical variables. Until now a significant amount of studies have focused on the influence of surgical technique on primary outcome, often leaving patient variables untouched. This study investigates the combined influence of patient and surgical variables through multivariate analysis.

Methods

Single-center retrospective cohort study. All patients who underwent primary ACL hamstring reconstruction within a 5-year period were included. Patient characteristics (gender, age, height, weight, BMI at time of surgery) and surgical variables (surgical technique, concomitant knee injury, graft diameter, type of femoral and tibial fixation) were collected. Patients were asked about Tegner Activity Scale (TAS), complications and revision surgery. Multivariate logistic regression was used to study risk factors. First graft failure and potential risk factors (patient and surgical) were univariately assessed. Risk factors with a p-value ≤ 0.05 were included in the multivariate model.

Results

Six hundred forty-seven primary ACL hamstring reconstructions were included. There were 41 graft failures (failure rate 6.3%). Patient gender, age, height and preoperative TAS had a significant influence on the risk of failure in the univariate analysis. The multivariate analyses showed that age and sex remained significant independent risk factors. Patients with a failed ACL reconstruction were younger (24.3 vs 29.4 years, OR 0.937), with women at a lower risk for failure of their ACL reconstruction (90.2% males vs 9.8% females, female OR 0.123). ACL graft diameter and other surgical variables aren’t confounders for graft failure.

Conclusion

This study shows that patient variables seem to have a larger influence on the failure rate of ACL hamstring reconstructive surgery than surgical variables. Identification of the right patient variables can help us make more informed decisions for our patients and create patient-specific treatment protocols. Young men’s higher risk of failure suggests that these patients may benefit from a different reconstruction technique, such as use of a patellar tendon or combined ligament augmentation.

Level of evidence

Retrospective cohort III.
Epidemiological profile of anterior cruciate ligament injuries in a tertiary referral trauma center of Nepal
Authors: Joshi Amit , Singh Nagmani , Basukala Bibek , Bista Rohit , Maharjan Bibek , Pradhan Ishor
Published: June 2022

Background

Sports related injuries are the leading cause of Anterior Cruciate Ligament (ACL) tear in the Western world. Although professional and recreational sporting activities are increasing in Nepal, they are not as common and prevalent in comparison to western world. In contrast, Road Traffic Accident (RTA) is a very common cause of knee injuries in Nepal. Although there are some studies from Nepal mentioning Road Traffic Accidents (RTAs) as the most common cause of ACL injury, no specific studies have primarily investigated the epidemiological and demographic profile of ACL injured patients from this region. we aimed to understand the epidemiological and demographic profile of ACL injured patients and evaluate the mode of injury in a tertiary referral trauma center of Nepal.

Methods

This was a retrospective descriptive study of a hospital cohort conducted from February 2018 to January 2020. Electronic details were retrieved, telephone interviews conducted and data analysis was done using descriptive analysis on the patients from the fore mentioned dates to complete demographic and epidemiological information.

Results

A total of 237 patients were enrolled in this study. Among these, 120 patients (50.6%) fell into the age group of 15–30 years with a male to female ratio of 2.7:1. A RTA was the most common cause of ACL injury (38.8%), followed by sports-related injuries in 33.3% and falls in 16.5% of patients. The most common mode of RTA was a two-wheeler accident, and football was the most common sport causing ACL injuries. Sports injury was more common in patients below 30 years of age (OR = 3.5, 95% CI [2.2, 5.7]), whereas RTA was more common in patients above 30 years of age. Sports was the cause of ACL injury in 55.5% of students and RTAs was the commonest cause of ACL injury in office workers.

Conclusion

Overall males were more frequently injured than females. Road traffic accidents were the most common cause of ACL injury in our subset of patients. Two-wheeler riders were the most commonly injured patients. Sport was the commonest cause of ACL injury in patients below 30 years, and RTA was common in patients above 30 years of age. Sports were the commonest cause of ACL injury in students, while RTA was the most common cause in office workers.
Testing delivery of components of cognitive behavioral therapy for insomnia to breast cancer survivors by smart speaker: a study protocol
Authors: Starling Claire M. , Greenberg Daniel , Zhou Eric , Lewin Daniel , Morrow Allison S. , Lieberman Daniel , Shaw Callen , Arem Hannah
Published: June 2022

Background

Insomnia is common in breast cancer survivors (BCS), affecting an estimated 30–50% of the 3.8 million BCS in the US. Insomnia is associated with health consequences for cardiometabolic and immune systems, neurobehavioral function, depression, fatigue, and quality of life and may put BCS at particular risk. While pharmacotherapy for insomnia may address symptoms in the short-term, cognitive behavioral therapy for insomnia (CBT-I) is considered the gold standard insomnia treatment. We describe our protocol to determine the efficacy of voice-activated delivery of CBT-I components on insomnia symptoms compared to a sleep education control among BCS.

Methods

We will conduct a 6-week, randomized controlled trial with two arms. Intervention arm participants will receive a smart speaker device and will be asked to engage with the program daily, using a voice-activated speaker with an accompanying smart-phone app. Control participants will have access to a website with basic information about CBT-I, sleep, and breast cancer survivorship and will be asked to engage with the website as desired.

Discussion

Our primary outcome is the Insomnia Severity Index total score. Secondary outcomes include sleep diary outcomes (sleep efficiency, wake after sleep onset, sleep onset latency, total sleep time, and sleep quality). This study will provide evidence on a promising modality to deliver elements of CBT-I for BCS experiencing insomnia.

Trial Registration ClinicalTrials.gov NCT05233800 Released 3/25/2022.
Discriminating TB lung nodules from early lung cancers using deep learning
Authors: Tan Heng , Bates Jason H. T. , Matthew Kinsey C.
Published: June 2022

Background

In developing countries where both high rates of smoking and endemic tuberculosis (TB) are often present, identification of early lung cancer can be significantly confounded by the presence of nodules such as those due to latent TB (LTB). It is very challenging to distinguish lung cancer and LTB without invasive procedures, which have their own risks of morbidity and even mortality.

Methods

Our method uses a customized VGG16-based 15-layer 2-dimensional deep convolutional neural network (DNN) architecture with transfer learning. The DNN was trained and tested on sets of CT images set extracted from the National Lung Screening Trial and the National Institute of Allergy and Infectious Disease TB Portals. Performance of the DNN was evaluated under locked and step-wise unlocked pretrained weight conditions.

Results

The DNN with unlocked pretrained weights achieved an accuracy of 90.4% with an F score of 90.1%.

Conclusions

Our findings support the potential for a DNN to serve as a noninvasive screening tool capable of reliably detecting and distinguishing between lung cancer and LTB.
Supporting family care: a scoping app review
Authors: Bidenko Katharina , Bohnet-Joschko Sabine
Published: June 2022

Background

Mobile applications (apps) may provide family caregivers of people with chronic diseases and conditions with access to support and good information. However, thorough understanding of how these apps meet the main needs and requirements of the users is currently lacking. The aim of this study was to review the currently available apps for family caregivers and evaluate their relevance to main domains of caregiving activities, caregivers’ personal needs, and caregivers’ groups found in previous research on family caregivers.

Methods

We conducted a scoping review on English-language and German-language apps for family caregivers on two major app stores: Google Play Store and iOS App Store. Apps were included if the main target group were family caregivers. Data were extracted from the app descriptions provided by the app producers in the app stores.

Results

The majority of the apps was designed to assist caregivers in their caregiving activities. Apps were rarely tailored to specific groups of family caregivers such as young carers and their needs. Further, apps addressing caregivers’ personal health, financial security, and work issues were scarce. Commercial apps dominated the market, often intermediating paid services or available for users of specific hardware. Public and non-profit organizations provided best-rated and free-of-charge apps but had a very limited range of services with focus on caregivers’ health and training.

Conclusions

Our results indicate that current apps for family caregivers do not distinguish specific groups of family caregivers, also they rarely address caregivers’ personal needs.
Pinpointing novel risk loci for Lewy body dementia and the shared genetic etiology with Alzheimer’s disease and Parkinson’s disease: a large-scale multi-trait association analysis
Authors: Guo Ping , Gong Weiming , Li Yuanming , Liu Lu , Yan Ran , Wang Yanjun , Zhang Yanan , Yuan Zhongshang
Published: June 2022

Background

The current genome-wide association study (GWAS) of Lewy body dementia (LBD) suffers from low power due to a limited sample size. In addition, the genetic determinants underlying LBD and the shared genetic etiology with Alzheimer’s disease (AD) and Parkinson’s disease (PD) remain poorly understood.

Methods

Using the largest GWAS summary statistics of LBD to date (2591 cases and 4027 controls), late-onset AD (86,531 cases and 676,386 controls), and PD (33,674 cases and 449,056 controls), we comprehensively investigated the genetic basis of LBD and shared genetic etiology among LBD, AD, and PD. We first conducted genetic correlation analysis using linkage disequilibrium score regression (LDSC), followed by multi-trait analysis of GWAS (MTAG) and association analysis based on SubSETs (ASSET) to identify the trait-specific SNPs. We then performed SNP-level functional annotation to identify significant genomic risk loci paired with Bayesian fine-mapping and colocalization analysis to identify potential causal variants. Parallel gene-level analysis including GCTA-fastBAT and transcriptome-wide association analysis (TWAS) was implemented to explore novel LBD-associated genes, followed by pathway enrichment analysis to understand underlying biological mechanisms.

Results

Pairwise LDSC analysis found positive genome-wide genetic correlations between LBD and AD (rg = 0.6603, se = 0.2001; P = 0.0010), between LBD and PD (rg = 0.6352, se = 0.1880; P = 0.0007), and between AD and PD (rg = 0.2136, se = 0.0860; P = 0.0130). We identified 13 significant loci for LBD, including 5 previously reported loci (1q22, 2q14.3, 4p16.3, 4q22.1, and 19q13.32) and 8 novel biologically plausible genetic associations (5q12.1, 5q33.3, 6p21.1, 8p23.1, 8p21.1, 16p11.2, 17p12, and 17q21.31), among which APOC1 (19q13.32), SNCA (4q22.1), TMEM175 (4p16.3), CLU (8p21.1), MAPT (17q21.31), and FBXL19 (16p11.2) were also validated by gene-level analysis. Pathway enrichment analysis of 40 common genes identified by GCTA-fastBAT and TWAS implicated significant role of neurofibrillary tangle assembly (GO:1902988, adjusted P = 1.55 × 10−2).

Conclusions

Our findings provide novel insights into the genetic determinants of LBD and the shared genetic etiology and biological mechanisms of LBD, AD, and PD, which could benefit the understanding of the co-pathology as well as the potential treatment of these diseases simultaneously.
Hepatitis B virus virion secretion is a CRM1-spike-mediated late event
Authors: Su Pei-Yi , Yen Shin-Chwen Bruce , Yang Ching-Chun , Chang Chih-Hsu , Lin Wen-Chang , Shih Chiaho
Published: June 2022

Background

Hepatitis B virus (HBV) is a major human pathogen worldwide. To date, there is no curative treatment for chronic hepatitis B. The mechanism of virion secretion remains to be investigated. Previously, we found that nuclear export of HBc particles can be facilitated via two CRM1-specific nuclear export signals (NES) at the spike tip.

Methods

In this study, we used site-directed mutagenesis at the CRM1 NES, as well as treatment with CRM1 inhibitors at a low concentration, or CRM1-specific shRNA knockdown, in HBV-producing cell culture, and measured the secretion of various HBV viral and subviral particles via a native agarose gel electrophoresis assay. Separated HBV particles were characterized by Western blot analysis, and their genomic DNA contents were measured by Southern blot analysis. Secreted extracellular particles were compared with intracellular HBc capsids for DNA synthesis and capsid formation. Virion secretion and the in vivo interactions among HBc capsids, CRM1 and microtubules, were examined by proximity ligation assay, immunofluorescence microscopy, and nocodazole treatment.

Results

We report here that the tip of spike of HBV core (HBc) particles (capsids) contains a complex sensor for secretion of both HBV virions and naked capsids. HBV virion secretion is closely associated with HBc nuclear export in a CRM1-dependent manner. At the conformationally flexible spike tips of HBc particles, NES motifs overlap extensively with motifs important for secretion of HBV virions and naked capsids.

Conclusions

We provided experimental evidence that virions and naked capsids can egress via two distinct, yet overlapping, pathways. Unlike the secretion of naked capsids, HBV virion secretion is highly CRM1- and microtubule-dependent. CRM1 is well known for its involvement in nuclear transport in literature. To our knowledge, this is the first report that CRM1 is required for virion secretion. CRM1 inhibitors could be a promising therapeutic candidate for chronic HBV patients in clinical medicine.
Immuno-activated mesenchymal stem cell living electrospun nanofibers for promoting diabetic wound repair
Authors: Gao Shaoying , Chen Tao , Wang Zhen , Ji Ping , Xu Lin , Cui Wenguo , Wang Ying
Published: June 2022

Diabetic wound is the leading cause of non-traumatic amputations in which oxidative stress and chronic inflammation are main factors affecting wound healing. Although mesenchymal stem cells (MSCs) as living materials can promote skin regeneration, they are still vulnerable to oxidative stress which limits their clinical applications. Herein, we have prepared (polylactic-co-glycolic acid) (PLGA) nanofibers electrospun with LPS/IFN-γ activated macrophage cell membrane. After defining physicochemical properties of the nanofibers modified by LPS/IFN-γ activated mouse RAW264.7 cell derived membrane (RCM-fibers), we demonstrated that the RCM-fibers improved BMMSC proliferation and keratinocyte migration upon oxidative stress in vitro. Moreover, bone marrow derived MSCs (BMMSCs)-loaded RCM-fibers (RCM-fiber-BMMSCs) accelerated wound closure accompanied by rapid re-epithelialization, collagen remodeling, antioxidant stress and angiogenesis in experimental diabetic wound healing in vivo. Transcriptome analysis revealed the upregulation of genes related to wound healing in BMMSCs when co-cultured with the RCM-fibers. Enhanced healing capacity of RCM-fiber-BMMSCs living material was partially mediated through CD200-CD200R interaction. Similarly, LPS/IFN-γ activated THP-1 cell membrane coated nanofibers (TCM-fibers) exhibited similar improvement of human BMMSCs (hBMMSCs) on diabetic wound healing in vivo. Our results thus demonstrate that LPS/IFN-γ activated macrophage cell membrane-modified nanofibers can in situ immunostimulate the biofunctions of BMMSCs, making this novel living material promising in wound repair of human diabetes.

Graphical Abstract
Outcomes of adolescent and young patients with hepatocellular carcinoma after curative liver resection: a retrospective study
Authors: Zhang Zheng-Yun , Guan Jiao , Wang Xin-Ping , Hao Di-Si , Zhou Zun-Qiang
Published: June 2022

Background

The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients.

Methods

We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018.

Results

The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30–40 (P = 0.047).

Conclusions

AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.
Secretion of miRNA-326-3p by senescent adipose exacerbates myocardial metabolism in diabetic mice
Authors: Lin Hao , Chen Xiaonan , Pan Jianan , Ke Jiahan , Zhang Alian , Liu Yangyang , Wang Changqian , Chang Alex Chia Yu , Gu Jun
Published: June 2022

Background

Adipose tissue homeostasis is at the heart of many metabolic syndromes such as diabetes. Previously it has been demonstrated that adipose tissues from diabetic patients are senescent but whether this contributes to diabetic cardiomyopathy (DCM) remains to be elucidated.

Methods

The streptozotocin (STZ) type 1 diabetic mice were established as animal model, and adult mouse ventricular myocytes (AMVMs) isolated by langendorff perfusion as well as neonatal mouse ventricular myocytes (NMVMs) were used as cell models. Senescent associated β galactosidase (SA-β-gal) staining and RT-qPCR were used to identify the presence of adipose senescence in diabetic adipose tissue. Senescent adipose were removed either by surgery or by senolytic treatment. Large extracellular vesicles (LEVs) derived from adipose tissue and circulation were separated by ultracentrifugation. Cardiac systolic and diastolic function was evaluated through cardiac ultrasound. Cardiomyocytes contraction function was evaluated by the Ionoptix HTS system and live cell imaging, mitochondrial morphology and functions were evaluated by transmission electron microscope, live cell fluorescent probe and seahorse analysis. RNA-seq for AMVMs and miRNA-seq for LEVs were performed, and bioinformatic analysis combined with RT-qPCR and Western blot were used to elucidate underlying mechanism that senescent adipose derives LEVs exacerbates myocardial metabolism.

Results

SA-β-gal staining and RT-qPCR identified the presence of adipose tissue senescence in STZ mice. Through surgical as well as pharmacological means we show that senescent adipose tissue participates in the pathogenesis of DCM in STZ mice by exacerbates myocardial metabolism through secretion of LEVs. Specifically, expression of miRNA-326-3p was up-regulated in LEVs isolated from senescent adipose tissue, circulation, and cardiomyocytes of STZ mice. Up-regulation of miRNA-326-3p coincided with myocardial transcriptomic changes in metabolism. Functionally, we demonstrate that miRNA-326-3p inhibited the expression of Rictor and resulted in impaired mitochondrial and contractile function in cardiomyocytes.

Conclusion

We demonstrate for the first time that senescent adipose derived LEVs exacerbates myocardial metabolism through up-regulated miRNA-326-3p which inhibits Rictor in cardiomyocytes. Furthermore, reducing senescence burden in adipose tissue is capable of relieving myocardial metabolism disorder in diabetes mellitus.