bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Prevalence of Left Lobe Atrophy in Long‐standing Extrahepatic Portal Vein Obstruction
Authors: Barreto Juliana C.C. , Sandy Natascha S. , Hessel Gabriel , de Alcantara Roberta V. , De Tommaso Adriana Maria A. , Yamada Roberto M. , Bellomo‐Brandão Maria Angela
Published: July 2021

Objectives:

The aim of this study was to describe long‐term changes in standard blood tests and ultrasound (US) findings in pediatric patients with Extrahepatic Portal Vein Obstruction (EHPVO) who have not undergone Meso‐Rex Bypass (MRB) surgery.

Methods:

US, laboratory, and endoscopic data of 77 patients were analyzed and compared at 2 different points in time: at initial workup and at most recent follow‐up. Differences were assessed using McNemar and Wilcoxon tests, while correlations were evaluated using generalized estimating equations.

Results:

Upper gastrointestinal bleeding was the most frequent initial manifestation of EHPVO, in 45.4% of subjects. The mean age at diagnosis was 4.3 years. Seventy‐four percentage had a previous history of umbilical catheterization and/or neonatal sepsis. Over time, there was a significant increase in the prevalence of leukopenia, thrombocytopenia, and, interestingly, of left lobe atrophy (LLA), even though the number of esophageal varices and the need for endoscopic interventions reduced. A significant correlation was found between history of umbilical catheterization and LLA, splenomegaly and LLA, and gallbladder wall thickening and LLA. Overall, the number of patients with cholelithiasis at initial workup was low (and therefore, not analyzed with inferential statistics); however, we observed a relative increase over time.

Conclusions:

In this cohort of patients with EHPVO followed over more than 8 years without treatment with MRB, we report the novel finding of a significant increase in the prevalence of LLA over time. LLA correlated with past medical history of umbilical catheterization, and findings of splenomegaly and gallbladder wall thickening. We propose that that LLA should be further explored as a marker of portal hypertension, particularly in the context of a history of umbilical catheterization.
A Descriptive Study of Resiliency and Health in Practicing Nurses
Authors: Stallings Welden Lois M. , Kalb Elizabeth , Willegal Kate , Chen Chen , White Ann
Published: July 2021

OBJECTIVES

The aim of this study was to identify the degree of resilience and self-perceived physical and mental health in practicing nurses.

BACKGROUND

Stressors and challenges of everyday demands influence resilience and well-being in acute care nurses.

METHODS

Nurses were surveyed using the Connor-Davidson Resilience Scale and PROMIS Global Health. One sample t test compared the study group to the general population mean of resiliency, physical and mental health scores. Linear regression analysis identified factors associated with resiliency.

RESULTS

Of the 859 practicing nurses in the sample, most were female and White, had a BSN or associate of science in nursing degree (55.2%, 30.0%) and more than 10 years of experience (57.1%), and worked in direct patient care (77.0%). Nurses had low resiliency (P < .0001) and physical health (P = .0037). Well-being factors included 2 or more missed days/shifts in 3 months (P < .001), thoughts of quitting (P = .003), and perceptions that workload was too much (P < .001).

CONCLUSIONS

Self-perceived physical and mental health was significantly associated with the degree of resilience.
Analgesic effect of perineural local anesthetics, steroids, and conventional medical management for trauma and compression-related peripheral neuropathic pain: a retrospective cohort study
Authors: Bhatia Anuj , Bril Vera , Brull Richard T. , Perruccio Anthony V. , Wijeysundera Duminda N. , Lau Johnny , Gandhi Rajiv , Mahomed Nizar , Davis Aileen M.
Published: July 2021

Introduction:

Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in relieving this type of pain is unclear.

Objectives:

The objectives of this retrospective study were to determine the analgesic benefits of adding a combination of perineural local anesthetic and steroids (LA-S) to CMM compared with CMM alone in patients who had moderate-to-severe refractory NP after trauma to the ankle and the foot.

Methods:

Health care records of 60 patients in exposed (3 injections of perineural LA-S at weekly intervals with CMM) and 60 in unexposed (CMM) cohorts were reviewed. Data on patient characteristics, pain, and mental and physical function were extracted at baseline and at the postintervention follow-up. Data were analyzed to evaluate analgesic benefit from the study interventions and the impact of baseline characteristics.

Results:

Perineural LA-S with CMM cohort had lower pain numerical rating scale scores at 1 to 3 months after the intervention as compared to the CMM alone cohort (5.50 [interquartile range 4.00–7.00] and 7.00 [interquartile range 5.00–8.00], respectively; P < 0.01). However, multivariable analysis did not show an independent beneficial analgesic effect with the addition of perineural LA-S to CMM compared with CMM alone. A greater severity of preintervention catastrophizing (each unit increase in pain catastrophizing score increased pain score at follow-up by 0.04, 95% confidence interval: 0.01–0.07) was associated with reduction in the analgesic benefit.

Conclusion:

Perineural local anesthetic and steroid injections do not confer an analgesic benefit for trauma- or compression-related peripheral NP.
Proposal for the Fusion of Ultrasound and Computed Tomography Images for Image Shift Correction in Craniomaxillofacial Soft Tissue Surgery
Authors: Yang Chengshuai , Zhang Yong , Wu Jinyang , Zhang Shilei
Published: July 2021

Surgical navigation has greatly improved the accuracy of craniomaxillofacial bone surgery and is widely used in the clinic. However, during surgery, craniomaxillofacial soft tissue is always deformed due to traction and compression, which leads to intraoperative image drift. This, in turn, impacts navigation accuracy. In order to improve navigation accuracy, this technical note presents a preliminary proposal for fusion imaging technology, which combines ultrasound and computed tomography to address navigational image drift in craniomaxillofacial soft tissue surgery.
Submandibular Gland Excision in Pediatric Patients
Authors: Kalmar Christopher L. , Patel Vijay A. , Zapatero Zachary D. , Kosyk Mychajlo S. , Taylor Jesse A. , Swanson Jordan W.
Published: July 2021

Introduction:

Children who require submandibular gland excision for ptyalism often have multiple associated comorbidities, including neurodevelopmental disorders and respiratory risk factors. The purpose of this study is to utilize a large multicenter database to elucidate the perioperative profile of submandibular gland excision in children, with particular focus on children who require submandibular gland excision for ptyalism.

Methods:

The American College of Surgeons National Surgical Quality Improvement Program Pediatric dataset was queried for submandibular gland excision performed from 2012 through 2018. Indications were subclassified based on International Classification of Disease (ICD)-9 and ICD-10 codes. Complications, readmissions, and reoperations were analyzed with appropriate statistics.

Results:

During the study interval, 304 pediatric patients underwent submandibular gland excision, which was mostly performed for ptyalism (56.9%), followed by inflammatory conditions (20.7%). Patients requiring submandibular gland excision for ptyalism were significantly younger (P < 0.001) and underwent significantly longer procedures (P < 0.001). Ptyalism was associated with significantly higher related adverse events (P = 0.010), related readmission (P = 0.013), and medical complications (P = 0.013), which included a significantly higher risk of pneumonia (P = 0.050). Children with ptyalism had significantly higher rates of overall respiratory comorbidities (P < 0.001), including chronic lung disease (P < 0.001), supplemental oxygen support (P < 0.001), tracheostomy (P < 0.001), and ventilator dependence (P < 0.001). Patients undergoing submandibular gland excision for benign (P all ≥ 0.082) and malignant (P all ≥ 0.565) neoplasms did not have significantly higher rates of any indexed postoperative adverse event.

Conclusions:

Children requiring submandibular gland excision for ptyalism represent a unique cohort than those requiring excision for other indications, with significantly higher burden of preoperative risk factors, intraoperative durations, and postoperative adverse events.
Successful Microsurgical Scalp Replantation Utilizing Loupe Magnification
Authors: Chopan Mustafa , Leyngold Mark , Ching Jessica
Published: July 2021

Total scalp avulsion is a rare injury that poses a unique reconstructive challenge. Microsurgical replantation is considered the first-line choice; yet anastomotic efforts may be strained to find suitable recipient and target vessels. Concomitant injuries may also delay or hinder operative intervention. These complex scenarios are difficult to navigate and necessitate multidisciplinary input to optimize outcomes. As such, the authors present an illustrative case report of a total scalp avulsion injury that underwent successful microsurgical replantation. This report highlights the novel use of loupe magnification in scalp replantation and reviews technical and clinical nuances that facilitate a favorable reconstruction.
A Severe Case of Biparietal Thinning in a Medieval Skull From a Northern Italy Necropolis
Authors: Tonina Enrica , Larentis Omar , Tesi Chiara , Fusco Roberta , Campagnolo Monica , Licata Marta
Published: July 2021

This study aims at presenting a case of symmetrical and bilateral thinning observed in a skull belonging to the skeleton of a mature woman from the medieval cemetery of Caravate (north Italy). Macroscopical, radiological, and histological analyses were performed to investigate the condition. The analyses allowed us to detect a progressive loss of both the outer table and the diploe, and the sparing of the inner table. As a controversial condition in the clinical and paleopathological literature, this case poses some difficulties in discussing the differential diagnosis. However, the sex determination, estimation of the age-at-death and different characteristics observed at the level of the postcranial bones, in particular the fractures recorded on different vertebral bodies, allowed us to correlate the biparietal thinning found in this subject to ageing and osteoporosis.
Indications and Limitations of Carbonated Calcium Phosphate Cement for Secondary Contouring Cranioplasty: A Long-Term Institutional Experience
Authors: Shakir Sameer , Kalmar Christopher L. , Yang Robin , Taylor Jesse A. , Bartlett Scott P.
Published: July 2021

The authors describe our long-term institutional experience utilizing carbonated calcium phosphate (CCP) cement for secondary cranioplasty refinements with the goals to

The authors conducted a retrospective cohort study of patients undergoing secondary cranioplasty for forehead reshaping utilizing CCP between June 2007 and August 2018. Exclusion criteria included < 3-month follow-up. The primary outcome was aesthetic forehead correction determined by Whitaker classification, while secondary outcomes included complications and reoperations. In total, 107 patients met inclusion with a median age of 15.5 years. The majority of bony deficits were limited to the frontal region (90.7%), required onlay application (87.7%) of large (96.0 cm2) partial thickness (85.7%) cranial defects, in a clean setting (99.0%), and ASA grade II (69.7%). Median Whitaker classification decreased from 2.3 [IQR: 2, 2.3] preoperatively to 1.0 [1.0, 1.3] postoperatively (P < 0.01). There was no difference in Whitaker classification between early and late postoperative timepoints (P < 0.17). The complication rate was 13.2%, with the majority related to infection (5/14). Factors associated with complications included frontal sinus proximity (OR 3.6, P < 0.04) and the use of interposition titanium mesh for full-thickness reconstruction (OR 6.4, P < 0.02). CCP remains an effective alloplastic bone substitute with a complication rate of 13.2% in patients undergoing secondary, onlay cranioplasty. Early postoperative Whitaker classification may predict long-term aesthetic results. Complications may arise years following implantation, warranting long-term follow-up.
One-Year Stability of LeFort I Advancement in Patients With Complete Cleft Lip and Palate Using a Standardized Clinical and Surgical Protocol
Authors: Parikh Vrajkumar , Gonchar Marina , Gibson Travis L. , Grayson Barry H. , Cutting Court B. , Shetye Pradip R.
Published: July 2021

Aim:

To assess treatment outcome and 1-year stability of LeFort I advancement in patients with complete cleft lip and palate.

Methods:

Thirty-five patients (age 20.65 ± 2.20 years) with unilateral (n = 25) or bilateral (n = 10) complete cleft lip and palate who underwent LeFort I advancement were included.

Lateral cephalograms before surgery (T1), immediately postsurgery (T2), and at 1-year follow-up (T3) were superimposed, and the position of anterior nasal spine (ANS), A-point, and U1 Tip assessed using an x, y coordinate system. Differences between landmark positions at the 3-time points were analyzed using paired sample t-tests, with a significance defined as α ≤ 0.05.

Results:

The mean surgical advancement in the horizontal direction (T2-T1) was 6.50 ± 2.62 mm at ANS (P < 0.001) and 7.05 ± 2.51 mm at A-point (P < 0.001). At a 1-year follow-up (T3-T2), the mean horizontal relapse at ANS was –1.41 ± 1.89 mm (P < 0.001) and –0.79 ± 1.48 mm at A-point (P 0.003). Mean horizontal relapse was 21.7% and 11% of surgical advancement when assessed at ANS and A-point, respectively. The central incisor tip position remained stable during the postsurgical period (0.12 ± 2.11 mm, P 0.732). At A-point, the mean vertical surgical change (T2–T1) was –0.96 ± 2.57 mm (P < 0.001). No significant post-treatment (T3–T2) vertical changes were detected at ANS or A-point. Phenotypic stability was excellent, with all patients maintaining positive overjet at 1-year follow-up.

Conclusions:

LeFort I advancement in complete cleft lip and palate is stable, with less than a 2 mm relapse after 1-year. Surgical overcorrection by 10% to 20% is recommended to compensate for the expected skeletal relapse.
Local Skull Thinning is One of Risks for the Ruptured Arachnoid Cysts With Chronic Subdural Hematoma in Adults: Thirty-two Clinical Reports
Authors: Mao Xiang , Xu Long , Liu Weiming , Hao Shuyu , Liu Baiyun
Published: July 2021

Objective:

Chronic subdural hematomas (CSDHs) in young people are uncommon, rupture of arachnoid cysts (ACs) is one of the reasons for young patients. The detailed features of CSDHs associated with ACs remain poorly understood. The objective of this study is to analyze the characteristics of risks for the rupture of ACs with CSDH in Adults.

Methods:

The CT scans of 1231 patients who were diagnosed as CSDH were reviewed between Jan 2009 and Jan 2019 in the Department of Neurotrauma in Beijing Tian Tan Hospital, Capital Medical University/China National Clinical Research Center for Neurological Diseases. The clinical features, treatments, and prognosis of 32 patients with ACs were analyzed.

Results:

Ruptured ACs with CSDH were diagnosed in 32 patients in 1231 CSDH cases, which account for 2.60%. Headache was the commonest presenting symptom. According to the Takizawa’ classification, there were 22 cases for Type A, 9 for Type B and 1 for Type C. Thinning or external convex of the calvarium was demonstrated in 17/32 cases (53.1%). Thirty-one patients were treated with burr hole irrigation. Favorable outcomes were achieved in all patients.

Conclusions:

The presence of ACs should be taken into consideration in young and middle-aged patients with CSDH. For those patients were found ACs in conventional medical examination, especially those whose imaging examinations demonstrated thinning or external convex of the calvarium, it was crucial to remind them to avoid the occurrence of traumatic brain injury (TBI). Burr hole irrigation is still the preferred treatment for ruptured ACs with CSDH.
HPi: A Novel Parameter to Predict Graft-related Outcome in Adult Living Donor Liver Transplant
Authors: Singh Akanand , Singhal Saurabh , Venuthurimilli Arun , Pareek Shishir , Maung Pyone Maung , Aung Thet Htoo , Garg Hitendra Kumar , Vohra Sandeep , Sahni Reeti , Goyal Neerav
Published: July 2021

Background.

Portal hyperperfusion is frequently associated with early allograft dysfunction (EAD). It is imperative to identify patients who would require portal inflow modulation. We aimed to identify factors associated with hyperperfusion-related graft injury and develop a predictive index for the same.

Methods.

Prospectively maintained database was queried to identify 135 adult living donor liver transplant recipients between September 2016 and July 2020. According to the calculated sample size, 96 patients were randomly selected for “test cohort”. The remaining 39 patients made the “validation cohort.” EAD was defined according to the A2ALL study. “Hyperperfusion index (HPi),” defined as posttransplant portal pressure gradient (ΔP
post)/graft-to-recipient splenic volume ratio (GRSVR), was devised on the basis of laws of flow dynamics and regression analysis.

Results.

Overall, 40 patients (29.6%) had EAD, six 90-d mortalities (4.4%) were attributable to EAD. In the test cohort, EAD patients (n = 29, 30.2%) had lower GRSVR (1.00 versus 2.22, P < 0.001), higher ΔP
post (14.8 versus 11.9, P = 0.004), and HPi (20.89 versus 8.67, P < 0.001). Multivariate analysis revealed GRSVR, ΔP
post, and HPi as significant factors to predict EAD. Receiver operating characteristic determined cutoff of HPi ≥9.97 could predict EAD with sensitivity of 90% and specificity of 73% (F-score = 0.712). HPi ≥16.25 predicted 90-d mortality with sensitivity of 100% and specificity of 78.9%. Patients with higher HPi had delayed graft-related recovery. Non-EAD patients had a higher 1-y (96% versus 79%) and 2-y (88% versus 79%) survival. The cutoff of HPi was validated well in the validation cohort (F-score = 0.645) (Hosmer-Lemeshow test, P = 0.89).

Conclusions.

While predicted GRSVR may help identify at-risk patients preoperatively, intraoperatively calculated HPi is more accurate in identifying patients who would require portal inflow modulation. Achieving an HPi below target cutoff significantly decreases the risk of EAD even in low-GRSVR patients.
Exceptional ancient DNA preservation and fibre remains of a Sasanian saltmine sheep mummy in Chehrābād, Iran
Authors: Rossi Conor , Ruß-Popa Gabriela , Mattiangeli Valeria , McDaid Fionnuala , Hare Andrew J. , Davoudi Hossein , Laleh Haeedeh , Lorzadeh Zahra , Khazaeli Roya , Fathi Homa , Teasdale Matthew D. , A'ali Abolfazl , Stöllner Thomas , Mashkour Marjan , Daly Kevin G.
Published: July 2021

Mummified remains have long attracted interest as a potential source of ancient DNA. However, mummification is a rare process that requires an anhydrous environment to rapidly dehydrate and preserve tissue before complete decomposition occurs. We present the whole-genome sequences (3.94 X) of an approximately 1600-year-old naturally mummified sheep recovered from Chehrābād, a salt mine in northwestern Iran. Comparative analyses of published ancient sequences revealed the remarkable DNA integrity of this mummy. Hallmarks of postmortem damage, fragmentation and hydrolytic deamination are substantially reduced, likely owing to the high salinity of this taphonomic environment. Metagenomic analyses reflect the profound influence of high-salt content on decomposition; its microbial profile is predominated by halophilic archaea and bacteria, possibly contributing to the remarkable preservation of the sample. Applying population genomic analyses, we find clustering of this sheep with Southwest Asian modern breeds, suggesting ancestry continuity. Genotyping of a locus influencing the woolly phenotype showed the presence of an ancestral ‘hairy’ allele, consistent with hair fibre imaging. This, along with derived alleles associated with the fat-tail phenotype, provides genetic evidence that Sasanian-period Iranians maintained specialized sheep flocks for different uses, with the ‘hairy’, ‘fat-tailed’-genotyped sheep likely kept by the rural community of Chehrābād's miners.
Scalable parametric encoding of multiple modalities
Authors: Banh David , Huang Alan
Published: July 2021

Abstract

A flexible model is introduced which shares ideas with the Autoencoder, Canonical Correlation Analysis, Singular Value Decomposition, and Procrustes Analysis. It is proposed to find relevant maps to transform multiple datasets of various types from one modality to another. Here, the Generative Encoder is used to transform spatial gene expression from breast tissue, to the images of histology tissue measured with Spatial Transcriptomics. The model is directly interpretable given all parameters are linked to the data space. It is scalable on Big Data, training reasonably on several thousand RGB images of 100 by 100 pixels in under an hour, which equates to 30,000 pixel features per sample image.
Online queries as a criterion for evaluation of the epidemiological status and effectiveness of COVID-19 epidemic control measures
Authors: Momynaliev K. T. , Khoroshun D. K. , Akimkin V. G.
Published: July 2021

Monitoring online queries can provide early and accurate information about the spread of COVID-19 in the population and about the effectiveness of COVID-19 epidemic control measures.

The purpose of the study

Assessment of significance of online queries regarding smell impairment to evaluate the epidemiological status and effectiveness of COVID-19 epidemic control measures.

Materials and methods

Weekly online queries from Yandex Russian users regarding smell impairment were analysed in regions and large cities of Russia from 16/3/2020 to 21/2/2021. A total of 81 regions of Russia and several large cities, such as Moscow, St. Petersburg, and Nizhny Novgorod, were included in the study.

Results

A strong positive direct correlation (r>0.7) was found between the number of smell-related queries in Yandex new cases of COVID-19 in 59 out of 85 Russian regions and large cities (70%). During the “first” peak of COVID-19 incidence in Russia (April-May 2020), the increase in the number of smell-related queries outpaced the increase in the number of new cases by 1-2 weeks in 23 out of 59 regions of Russia. During the “second” peak of COVID-19 incidence in Russia (October-December 2020), the increase in the number of smell-related queries outpaced the increase in the number of new cases by 1-2 weeks in 36 regions of Russia, including Moscow. We also estimated the increase in the query/new case ratio during the “second” peak of incidence for 45 regions. It was found that the query/new case ratio increased by more than 100% in 24 regions. The regions where the increase in queries was more than 160% compared to new infection cases during the “second” peak of incidence demonstrated significantly higher search activity related to levofloxacin than the regions where the increase in queries was lower than 160% compared to the increase in new infection cases.

Conclusion

The sudden interest in smell impairment and growing frequency of online queries among the population can be used as an indicator of the spread of coronavirus infection among the population as well as for evaluation of the effectiveness of COVID-19 epidemic control measures.
A reinforcement learning model to inform optimal decision paths for HIV elimination1
Authors: Khatami Seyedeh N. , Gopalappa Chaitra
Published: July 2021

The ‘Ending the HIV Epidemic (EHE)’ national plan aims to reduce annual HIV incidence in the United States from 38,000 in 2015 to 9,300 by 2025 and 3,300 by 2030. Diagnosis and treatment are two most effective interventions, and thus, identifying corresponding optimal combinations of testing and retention-in-care rates would help inform implementation of relevant programs. Considering the dynamic and stochastic complexity of the disease and the time dynamics of decision-making, solving for optimal combinations using commonly used methods of parametric optimization or exhaustive evaluation of pre-selected options are infeasible. Reinforcement learning (RL), an artificial intelligence method, is ideal; however, training RL algorithms and ensuring convergence to optimality are computationally challenging for large-scale stochastic problems. We evaluate its feasibility in the context of the EHE goal.

We trained an RL algorithm to identify a ‘sequence’ of combinations of HIV-testing and retention-in-care rates at 5-year intervals over 2015-2070, which optimally leads towards HIV elimination. We defined optimality as a sequence that maximizes quality-adjusted-life-years lived and minimizes HIV-testing and care-and-treatment costs. We show that solving for testing and retention-in-care rates through appropriate reformulation using proxy decision-metrics overcomes the computational challenges of RL. We used a stochastic agent-based simulation to train the RL algorithm. As there is variability in support-programs needed to address barriers to care-access, we evaluated the sensitivity of optimal decisions to three cost-functions.

The model suggests to scale-up retention-in-care programs to achieve and maintain high annual retention-rates while initiating with a high testing-frequency but relaxing it over a 10-year period as incidence decreases. Results were mainly robust to the uncertainty in costs. However, testing and retention-in-care alone did not achieve the 2030 EHE targets, suggesting the need for additional interventions. The results from the model demonstrated convergence. RL is suitable for evaluating phased public health decisions for infectious disease control.
CLPTM1L is a lipid scramblase involved in glycosylphosphatidylinositol biosynthesis
Authors: Wang Yicheng , Menon Anant K. , Maki Yuta , Liu Yi-Shi , Iwasaki Yugo , Fujita Morihisa , Guerrero Paula A. , Varón Silva Daniel , Seeberger Peter H. , Murakami Yoshiko , Kinoshita Taroh
Published: July 2021

Glycosylphosphatidylinositols (GPIs) are membrane anchors of many eukaryotic cell surface proteins. Biosynthesis of GPIs is initiated at the cytosolic face of the endoplasmic reticulum (ER) and the second intermediate, glucosaminyl-phosphatidylinositol (GlcN-PI), is translocated across the membrane to the lumenal face for later biosynthetic steps and attachment to proteins. The mechanism of the lumenal translocation of GlcN-PI is unclear. We report that Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L), an ER membrane protein of unknown function, is a lipid scramblase involved in GPI biosynthesis. Purified CLPTM1L scrambles GlcN-PI, PI, and several other phospholipids in vitro. Knockout of CLPTM1L gene in mammalian cultured cells partially decreased GPI-anchored proteins due to impaired usage of GlcN-PI, suggesting a major role of CLPTM1L in lumenal translocation of GlcN-PI.

One-Sentence Summary

CLPTM1L translocates glucosaminyl-phosphatidylinositol across the membrane during glycosylphosphatidylinositol biosynthesis.
Electronic “photoreceptors” enable prosthetic vision with acuity matching the natural resolution in rats
Authors: Wang Bing-Yi , Chen Zhijie Charles , Bhuckory Mohajeet , Huang Tiffany , Shin Andrew , Zuckerman Valentina , Ho Elton , Rosenfeld Ethan , Galambos Ludwig , Kamins Theodore , Mathieson Keith , Palanker Daniel
Published: July 2021

Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal cross-talk from neighboring electrodes. Local return electrodes within each pixel limit crosstalk, but can over-constrain the electric field, thus precluding efficient stimulation with subretinal pixels smaller than 50 μm. Here we demonstrate high-resolution prosthetic vision based on a novel design of a photovoltaic array, where field confinement is achieved dynamically, leveraging the adjustable conductivity of the diodes under forward bias to turn the designated pixels into transient returns. We validated computational modeling of the field confinement in such an optically-controlled circuit by ex-vivo and in-vivo measurements. Most importantly, using this strategy, we demonstrated that the grating acuity with 40 μm pixels matches the pixel pitch, while with 20 μm pixels, it reaches the 28 μm limit of the natural visual resolution in rats. This method enables customized field shaping based on individual retinal thickness and distance from the implant, paving the way to prosthetic vision with acuity as high as 20/80 in atrophic macular degeneration.
Core bone diameter in an organic implant-less technique affecting the biomechanical properties of the anterior cruciate ligament fixation; an in-vitro study
Authors: Mohseni Mahdi , Nourani Amir , Korani Hossein , Moeinnia Hadi , Borjali Amirhossein , Ghias Narges , Chizari Mahmoud
Published: July 2021

Background

Bone and site hold tendon inside (BASHTI) is an implant-less technique that can solve some of the problems associated with other anterior cruciate ligament (ACL) reconstructive methods. This study aims to investigate the effect of core bone diameter variation on the biomechanical properties of a reconstructed ACL using BASHTI technique.

Methods

A number of 15 laboratory samples of reconstructed ACL were built using bovine digital tendons and Sawbones blocks. Samples were divided into three groups with different core bone diameters of 8 mm, 8.5 mm, and 9 mm. The double-stranded tendon size and bone tunnel diameter were 8 mm and 10 mm, respectively. A loading scenario consisting of two cyclic loadings followed by a single cycle pull-out loading was applied to the samples simulating the after-surgery loading conditions to observe the fixation strength.

Results

Results showed that the core bone diameter had a significant effect on the failure mode of the samples (P = 0.006) and their fixation strength (P < 0.001). Also, it was observed that the engaging length and the average cyclic stiffness (ACS) of them were influenced by the core bone diameter significantly (engaging length: P = 0.001, ACS: P = 0.007), but its effect on the average pull-out stiffness was not significant (P = 0.053).

Conclusions

It was concluded that core bone diameter variation has a significant impact on the mechanical properties of ACL reconstruction when BASHTI technique is used, and it should be noted for surgeons who use BASHTI technique.

Abstract Figure

Highlights

A new implant-less technique was used to reconstruct anterior cruciate ligament.

Artificial bone and fresh animal soft tissue used to simulate the fixation process.

Loading condition were carefully chosen to simulate the post-operation.

Components geometry had direct effect on biomechanical properties of the fixation.

Optimum geometry was found trough an experimental examination.
Nuclear Factor I in neurons, glia and during the formation of Müller glia-derived progenitor cells in avian, porcine and primate retinas
Authors: El-Hodiri Heithem M. , Campbell Warren A. , Kelly Lisa E. , Hawthorn Evan C. , Schwartz Maura , Jalligampala Archana , McCall Maureen A. , Meyer Kathrin , Fischer Andy J.
Published: July 2021

The regenerative potential of Müller glia (MG) is extraordinary in fish, poor in chick and terrible in mammals. In the chick model, MG readily reprogram into proliferating Müller glia-derived progenitor cells (MGPCs), but neuronal differentiation is very limited. The factors that suppress the neurogenic potential of MGPCs in the chick are slowly being revealed. Isoforms of Nuclear Factor I (NFI) are cell-intrinsic factors that limit neurogenic potential; these factors are required for the formation of MG in the developing mouse retina (Clark et al., 2019) and deletion of these factors reprograms MG into neuron-like cells in mature mouse retina (Hoang et al., 2020). Accordingly, we sought to characterize the patterns of expression NFIs in the developing, mature and damaged chick retina. In addition, we characterized patterns of expression of NFIs in the retinas of large mammals, pigs and monkeys. Using a combination of single cell RNA-sequencing (scRNA-seq) and immunolabeling we probed for patterns of expression. In embryonic chick, levels of NFIs are very low in early E5 (embryonic day 5) retinal progenitor cells (RPCs), up-regulated in E8 RPCs, further up-regulated in differentiating MG at E12 and E15. NFIs are maintained in mature resting MG, microglia and neurons. Levels of NFIs are reduced in activated MG in retinas treated with NMDA and/or insulin+FGF2, and further down-regulated in proliferating MGPCs. However, levels of NFIs in MGPCs were significantly higher than those seen in RPCs. Immunolabeling for NFIA and NFIB closely matched patterns of expression revealed in different types of retinal neurons and glia, consistent with findings from scRNA-seq. In addition, we find expression of NFIA and NFIB through progenitors in the circumferential marginal zone at the far periphery of the retina. We find similar patterns of expression for NFIs in scRNA-seq databases for pig and monkey retinas. Patterns of expression of NFIA and NFIB were validated with immunofluorescence in pig and monkey retinas wherein these factors were predominantly detected in MG and a few types of inner retinal neurons. In summary, NFIA and NFIB are prominently expressed in developing chick retina and by mature neurons and glia in the retinas of chicks, pigs and monkeys. Although levels of NFIs are decreased in chick, in MGPCs these levels remain higher than those seen in neurogenic RPCs. We propose that the neurogenic potential of MGPCs in the chick retina is suppressed by NFIs.
The Burkholderia cenocepacia type VI secretion system effector TecA is a virulence factor during lung infection
Authors: Loeven Nicole A. , Perault Andrew I. , Cotter Peggy A. , Hodges Craig A. , Schwartzman Joseph D. , Hampton Thomas H. , Bliska James B.
Published: July 2021

Burkholderia cenocepacia (Bc) is a member of the Burkholderia cepacia complex (Bcc), a group of bacteria with members responsible for causing lung infections in cystic fibrosis (CF) patients. The most severe outcome of Bcc infection in CF patients is cepacia syndrome, a disease characterized by necrotizing pneumonia with bacteremia and sepsis. Bc is strongly associated with cepacia syndrome making it one of the most virulent members of the Bcc. Mechanisms underlying the pathogenesis of Bc in lung infections and cepacia syndrome remain to be uncovered. Bc is primarily an intracellular pathogen, and encodes the type VI secretion system (T6SS) anti-host effector TecA, which is translocated into host cells. TecA is a deamidase that inactivates multiple Rho GTPases, including RhoA. Inactivation of RhoA by TecA triggers assembly of the pyrin inflammasome, leading to secretion of proinflammatory cytokines such as IL-1β from macrophages. Previous work with the Bc clinical isolate J2315 showed that TecA increases immunopathology during acute lung infection in C57BL/6 mice and suggested that this effector acts as a virulence factor by triggering assembly of the pyrin inflammasome. Here, we extend these results using a second Bc clinical isolate, AU1054, to demonstrate that TecA exacerbates weight loss and lethality during lung infection in C57BL/6 mice and CF mice. Unexpectedly, pyrin was dispensable for TecA virulence activity in both mouse infection models. Our findings establish that TecA is a Bc virulence factor that exacerbates lung inflammation, weight loss, and lethality in a mouse lung infection model.

Importance

Bc is often considered the most virulent species in the Bcc because of its close association with cepacia syndrome in addition to its capacity to cause chronic lung infections in CF patients (Loutet and Valvano 2010). Prior to this study virulence factors of Bc important for causing lethal disease had not been identified in a CF animal model of lung infection. Results of this study describe a CF mouse model and its use in demonstrating that the T6SS effector TecA of Bc exacerbates inflammatory cell recruitment and weight loss and is required for lethality and thus acts as a key virulence factor during lung infection. This model will be important in further studies to better understand TecA’s role as a virulence factor and in investigating ways to prevent or treat Bc infections in CF patients. Additionally, TecA may be the founding member of a family of virulence factors in opportunistic pathogens.
Climate and mountains shaped human ancestral genetic lineages
Authors: Delser Pierpaolo Maisano , Krapp Mario , Beyer Robert , Jones Eppie R , Miller Eleanor F , Hovhannisyan Anahit , Parker Michelle , Siska Veronika , Vizzari Maria Teresa , Pearmain Elizabeth J. , Imaz-Rosshandler Ivan , Leonardi Michela , Somma Gian Luigi , Hodgson Jason , Tysall Eirlys , Xue Zhe , Cassidy Lara , Bradley Daniel G , Eriksson Anders , Manica Andrea
Published: July 2021

Extensive sequencing of modern and ancient human genomes has revealed that contemporary populations can be explained as the result of recent mixing of a few distinct ancestral genetic lineages1. But the small number of aDNA samples that predate the Last Glacial Maximum means that the origins of these lineages are not well understood. Here, we circumvent the limited sampling by modelling explicitly the effect of climatic changes and terrain on population demography and migrations through time and space, and show that these factors are sufficient to explain the divergence among ancestral lineages. Our reconstructions show that the sharp separation between African and Eurasian lineages is a consequence of only a few limited periods of connectivity through the arid Arabian peninsula, which acted as the gate out of the Arican continent. The subsequent spread across Eurasia was then mostly shaped by mountain ranges, and to a lesser extent deserts, leading to the split of European and Asians, and the further diversification of these two groups. A high tolerance to cold climates allowed the persistence at high latitudes even during the Last Glacial Maximum, maintaining a pocket in Beringia that led to the later, rapid colonisation of the Americas. The advent of food production was associated with an increase in movement2, but mountains and climate have been shown to still play a major role even in this latter period3,4, affecting the mixing of the ancestral lineages that we have shown to be shaped by those two factors in the first place.
Muscle effort is best minimized by the right-dominant arm in the gravity field
Authors: Poirier Gabriel , Lebigre Mélanie , Mourey France , Papaxanthis Charalambos , Gaveau Jeremie
Published: July 2021

The central nervous system (CNS) is thought to develop motor strategies that minimize various hidden criteria, such as end-point variance or effort. A large body of literature suggests that the dominant arm is specialized for such open-loop optimization-like processes whilst the non-dominant arm is specialized for closed-loop control. Building on recent results suggesting that the brain plans arm movements that takes advantage of gravity effects to minimize muscle effort, the present study tests the hypothesized superiority of the dominant arm motor system for effort minimization. Thirty participants (22.5 ± 2.1 years old; all right-handed) performed vertical arm movements between two targets (40° amplitude), in two directions (upwards and downwards) with their two arms (dominant and non-dominant). We recorded the arm kinematics and the electromyographic activity of the anterior and posterior deltoid to compare two motor signatures of the gravity-related optimization process; i.e., directional asymmetries and negative epochs on phasic muscular activity. We found that these motor signatures were still present during movements performed with the non-dominant arm, indicating that the effort-minimization process also occurs for the non-dominant motor system. However, these markers were reduced compared with movements performed with the dominant arm. This difference was especially prominent during downward movements, where the optimization of gravity effects occurs early in the movement. Assuming that the dominant arm is optimal to minimize muscle effort, as suggested by previous studies, the present results support the hypothesized superiority of the dominant arm motor system for effort-minimization.
Equatorial to Polar genomic variability of the microalgae Bathycoccus prasinos
Authors: Leconte Jade , Timsit Youri , Delmont Tom O. , Lescot Magali , Piganeau Gwenael , Wincker Patrick , Jaillon Olivier
Published: July 2021

Phytoplankton plays a fundamental role in the ecology of ocean systems and is the key player in the global carbon cycle. At a time of global warming, understanding the mechanisms of its adaptation to temperature is therefore of paramount importance. Cosmopolitan planktonic species abundant in different marine environments provide both a unique opportunity and an efficient methodological tool to study the genomic bases of their adaptation. This is the case for the eukaryotic picoalga Bathycoccus prasinos, whose genomic variability we chose to study in temperate and polar oceanic waters. Using multiple metagenomic datasets, we found that ~5% of B. prasinos genomic positions are variable, with an overwhelming majority of biallelic motifs. Cold and temperate waters are clearly associated with changes in variant frequencies, whereas in transitional waters we found more balanced polymorphism at most of these positions. Mesophilic and psychrophilic gene variants are distinguished by only a few amino acid changes located at positions critical for physical and functional protein properties. These results provide new information on the genomic diversity of a cosmopolitan eukaryotic planktonic specie and reveal “minimal mutational strategies” which finely tune the properties of specific proteins at different temperatures.
Statistics of the number of equilibria in random social dilemma evolutionary games with mutation
Authors: Duong Manh Hong , Han The Anh
Published: July 2021

In this paper, we study analytically the statistics of the number of equilibria in pairwise social dilemma evolutionary games with mutation where a game’s payoff entries are random variables. Using the replicator-mutator equations, we provide explicit formulas for the probability distributions of the number of equilibria as well as other statistical quantities. This analysis is highly relevant assuming that one might know the nature of a social dilemma game at hand (e.g., cooperation vs coordination vs anti-coordination), but measuring the exact values of its payoff entries is difficult. Our delicate analysis shows clearly the influence of the mutation probability on these probability distributions, providing insights into how varying this important factor impacts the overall behavioural or biological diversity of the underlying evolutionary systems.
Stochastic model of T Cell repolarization during target elimination (II)
Authors: Hornak Ivan , Rieger Heiko
Published: July 2021

Cytotoxic T lymphocytes (T cells) and natural killer cells form a tight contact, the immunological synapse (IS), with target cells, where they release their lytic granules containing perforin/granzyme and cytokine containing vesicles. During this process the cell repolarizes and moves the microtubule organizing center (MTOC) towards the IS. In the first part of our work we developed a computational model for the molecular-motor-driven motion of the MT cytoskeleton during T cell polarization and analyzed effects of cortical sliding and capture-shrinkage mechanisms. Here we use this model to analyze the dynamics of the MTOC repositioning in situations in which a) the IS is in an arbitrary position with respect to the initial position of the MTOC and b) the T cell has two IS at two arbitrary positions. In the case of one IS, we found that the initial position determines which mechanism is dominant and that the time of repositioning does not rise monotonously with the MTOC-IS distance. In the case of two IS, we observe several scenarios that have also been reported experimentally: the MTOC alternates stochastically (but with a well defined average transition time) between the two IS; it wiggles in between the two IS without transiting to one of the two; or it is at some point pulled to one of the two IS and stays there. Our model allows to predict which scenario emerges in dependency of the mechanisms in action and the number of dyneins present. We report that the presence of capture-shrinkage mechanism at least in one IS is necessary to assure the transitions in every cell configuration. Moreover, the frequency of transitions does not decrease with the distance between the two IS and is the highest when both mechanisms are present in both IS.
Neo-sex chromosome evolution shapes sex-dependent asymmetrical introgression barrier
Authors: Wang Silu , Nalley Matthew J. , Chatla Kamalakar , Aldaimalani Reema , MacPherson Ailene , Wei Kevin , Corbett Russ , Mai Dat , Bachtrog Doris
Published: July 2021

It is increasingly recognized that sex chromosomes are not only the “battlegrounds” between sexes, but also the “Great Walls” fencing-off introgression between diverging lineages. Here we describe conflicting roles of nascent sex chromosomes on patterns of introgression in an experimental hybrid swarm. Drosophila nasuta and D. albomicans are recently diverged, fully fertile sister species that have different sex chromosome systems. The fusion between an autosome (Muller CD) with the ancestral X and Y gave rise to neo-sex chromosomes in D. albomicans, while Muller CDs remains unfused in D. nasuta. We found that a large block containing overlapping inversions on the neo-sex chromosome stood out as the strongest barrier to introgression. Intriguingly, the neo-sex chromosome introgression barrier is asymmetrical in a sex-dependent manner. Female hybrids showed significant D. albomicans biased introgression on Muller CD (neo-X excess), while males showed heterosis with excessive (neo-X, D. nasuta Muller CD) genotypes. While the neo-Y is a more compatible pairing partner of the neo-X, it also shows moderate levels of degeneration and may thus be selectively disfavored, and sex ratio assay revealed heterospecific meiotic drive. We used a population genetic model to dissect the interplay of sex chromosome drive, heterospecific pairing incompatibility between the neo-sex chromosomes and unfused Muller CD, neo-Y disadvantage, and neo-X advantage in generating the observed neo-X excess in females and heterozygous (neo-X, D. nasuta Muller CD) genotypes in males. We show that moderate neo-Y disadvantage and D. albomicans specific meiotic drive are required to counteract the effect of heterospecific meiotic drive observed in our cross, in concert with pairing incompatibility and neo-X advantage to explain observed genotype frequencies. Together, this hybrid swarm between a young species pair shed light onto the dual roles of neo-sex chromosome evolution in creating a sex-dependent asymmetrical introgression barrier at species boundary.