bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Meeting Physical Activity Time-Intensity Guidelines With Ambulation, Quality of Life, and Inflammation in Claudication
Authors: Gardner Andrew W. , Montgomery Polly S. , Wang Ming , Shen Biyi , Zhang Shangming , Pomilla William A.
Published: April 2022

Purpose:

The aim of this investigation was to determine if meeting the 2018 physical activity (PA) time-intensity guidelines was associated with better ambulatory function, health-related quality of life (HRQoL), vascular function, and inflammation than failing to meet the guidelines in patients with peripheral artery disease and claudication. Second, we determined the optimal number of total steps/d and steps taken at moderate cadence needed to meet the PA time-intensity guidelines.

Methods:

Five hundred seventy-two patients were assessed on daily ambulatory activity for 1 wk with a step activity monitor, and were grouped according to whether they achieved <150 min of moderate-intensity PA/wk (group 1 = do not meet guidelines; n = 397) or whether they were above this threshold (group 2 = meet guidelines; n = 175).

Results:

Treadmill peak walking time (mean ± SD) was higher (P < .001) in group 2 (709 ± 359 sec) than in group 1 (427 ± 281 sec). The physical function HRQoL score was higher (P < .001) in group 2 (61 ± 22%) than in group 1 (44 ± 21%). High-sensitivity C-reactive protein was lower (P < .001) in group 2 (3.6 ± 4.5 mg/L) than in group 1 (5.9 ± 6.1 mg/L). Finally, ≥7675 total steps/d and ≥1660 steps/d at moderate cadence were optimal thresholds associated with meeting PA guidelines.

Conclusions:

Patients with claudication who meet the 2018 PA time-intensity guidelines for US adults had better ambulation, HRQoL, and vascular outcomes than those who failed to meet the PA guidelines. Patients with claudication best achieved the PA time-intensity guidelines by taking ≥7675 total steps/d, and ≥1660 steps/d at a moderate cadence.
Corneal Response to Scleral Contact Lens Wear in Keratoconus
Authors: Cagliari Cristina , Schor Paulo , Formentin Luiz , Lipener César , dos Santos Myrna Serapião , Oliveira Helena , Raulino Junior José Ney de Carvalho , de Freitas Denise
Published: April 2022

Objective:

To verify corneal alterations in patients with keratoconus who wear scleral contact lenses (ScCLs), focusing on corneal endothelial assessment.

Methods:

Scleral contact lenses were fitted in 22 patients with keratoconus. During a 90-day follow-up, patients were assessed in three visits: at baseline, after 30 days, and after 90 days. Patients underwent visual acuity measurement, slitlamp biomicroscopy of the anterior segment, specular microscopy of the corneal endothelium, corneal pachymetry, measurement of the clearance between the cornea and the lens, and follow-up of ectasia.

Results:

Variables related to endothelial morphology and pachymetry values did not change significantly over time. Central clearance measurements decreased in the 90-day period. No progression of corneal ectasia was observed, neither were infectious or inflammatory processes in the same period.

Conclusion:

Daily wear of ScCLs in patients with keratoconus was not associated with adverse effects on the cornea or endothelium over a period of 90 days nor was there evidence of disease progression. Central clearance values diminished over that period, but the significance of this observation remains unclear.
Outcomes and Complications in Patients With Hypermobile Ehlers–Danlos Syndrome Who Have Undergone Laser In Situ Keratomileusis Surgery
Authors: Gauthier Angela C. , Bower Kraig S. , Singman Eric L.
Published: April 2022

Purpose:

The purpose of this study was to determine the safety and outcomes of myopic laser in situ keratomileusis (LASIK) in patients who were secondarily diagnosed with hypermobile Ehlers–Danlos syndrome (EDS).

Methods:

We conducted a case series study on patients with hypermobile EDS who underwent myopic LASIK surgery. Visual acuity, manifest refraction, a full dilated eye examination, biometry measurements, and Scheimpflug imaging were performed in the Wilmer outpatient clinic.

Results:

There were 24 eyes of 12 patients included in this study. All participants were White women with a mean age of 46.58 years (SD 8.91 years). Participants were seen at an average of 13.83 years (SD 4.3 years, range 6–21 years) after undergoing LASIK. None of the patients in the series had a diagnosis of hypermobile EDS before LASIK surgery. Overall, 92% of patients were happy they got LASIK. The uncorrected distance visual acuity was 20/20 or better in 68% of eyes, and the best-corrected visual acuity was 20/20 or better in 92% of eyes. Manifest refraction was within 1 diopter of plano in 79% of patients. Dry eye symptoms were present in 83% of patients, and 46% of eyes had either punctate epithelial erosions or decreased tear break-up time. One of the 12 patients developed corneal ectasia in both eyes.

Conclusions:

Patients with hypermobile EDS are generally satisfied with myopic LASIK correction, with good visual acuity outcomes and low rates of myopic regression. However, the risk of corneal ectasia may prevent laser vision correction from being a viable treatment option in these patients. Further studies are needed to make a definitive recommendation.
Efficacy and Safety of Endoscopic Submucosal Dissection for Rectal Tumors Extending Versus Not to the Dentate Line
Authors: Zeng Qi-Shan , Zou Min , Nie Jiao , Yang Jia-Hui , Luo Zhen-Yi , Gan Hua-Tian
Published: April 2022

Goals:

To evaluate the outcomes of endoscopic submucosal dissection (ESD) for rectal tumors extending to the dentate line (RTDLs) compared with rectal tumors not extending to the dentate line (non-RTDLs).

Background:

There is limited composite data on the outcomes of ESD for RTDLs versus non-RTDLs.

Study:

We performed a systematic review and meta-analysis of studies that reported the clinical outcomes of ESD for RTDLs and non-RTDLs. Main outcomes were pooled estimated rates of en bloc/complete/curative resection, local recurrence, and incidence of bleeding, perforation, stricture, anal pain, and fever.

Results:

Six studies were enrolled, including 265 cases of RTDLs and 788 cases of non-RTDLs. The en bloc resection rate was comparable for RTDLs and non-RTDLs [odds ratio (OR), 1.04; 95% confidence interval (CI), 0.55-1.95; P=0.90]. The complete resection rate was significantly lower for RTDLs (OR, 0.59; 95% CI, 0.41-0.83; P=0.003), as well as the curative resection rate (OR, 0.57; 95% CI, 0.38-0.87; P=0.010). The rates of stricture, postoperative anal pain and local recurrence were significantly higher for RTDLs than non-RTDLs (OR, 3.07; 95% CI, 1.01-9.31; P=0.05) (OR, 42.10; 95% CI, 4.73-374.97; P=0.0008) (OR, 3.00; 95% CI, 1.13-7.96; P=0.03), but the higher rates of postoperative bleeding and fever for RTDLs were not significantly (OR, 1.33; 95% CI, 0.53-3.30; P=0.54) (OR, 2.23; 95% CI, 0.55-9.07; P=0.26), as well as its lower perforation rate (OR, 0.85; 95% CI, 0.27-2.63; P=0.78).

Conclusions:

Despite its inferior outcomes than non-RTDLs, ESD is still a feasible and safe treatment for RTDLs if appropriate lesions are treated by experienced operators.
An Evidence-based Practical Guide to Vaccination for Hepatitis B Virus
Authors: Jacobson Ira M. , Brown Robert S. , McMahon Brian J. , Perrillo Robert P. , Gish Robert
Published: April 2022

The hepatitis B virus (HBV) is highly infectious, with over 292 million chronically infected people worldwide and up to 2.4 million in the United States. Following infection, clinically silent liver damage can ensue, but symptoms or signs of advanced disease, including cirrhosis and hepatocellular carcinoma, can take decades to emerge. HBV has the heaviest public health burden of all hepatitis viruses and has now surpassed other major communicable diseases (eg, HIV, diarrheal disease, malaria, tuberculosis) as a leading cause of death globally. Preventing transmission is essential, and efforts are in place to reinforce screening, vaccination, and routine follow-up. Three safe and effective vaccines are available in the United States and other countries for HBV prevention, and the benefits of vaccination in preventing infection and its sequelae have been substantiated. For the first time in over 25 years, a new Food and Drug Administration-approved vaccine is available that offers a high degree of immunogenicity after 2, rather than 3, injections. Persistent challenges include the underutilization of vaccination, choice of vaccine, incomplete vaccinations, varying needs in different populations, management of nonresponders or those with undocumented or incompletely documented vaccination courses, and questions about whether and when booster injections may be needed. A panel of US academic hepatologists with expertise and experience in preventing and managing HBV infection have collaborated to write this practical clinical paper intended to guide clinicians in vaccinating for HBV and address questions that regularly arise in the clinic.
The Wet Suction Technique Enhances the Diagnostic Efficacy and Aspirate Quality of EUS-FNA for Solid Lesions
Authors: Chen Dafan , Ren Yingchun , Chen Sumin , Jin Yubiao , Xie Haoran , Yu Lanting , Peng Kui , Xia Youchen , Pan Dan , Lu Jiawei , Lu Lungen , Wan Xinjian , Hu Duanmin , Li Baiwen
Published: April 2022

Goals:

To comprehensively compare the wet suction technique with the conventional dry suction technique for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in solid lesions.

Background:

Optimal suction techniques for EUS-FNA remain uncertain when approaching solid lesions.

Study:

We performed a retrospective study of EUS-FNA at 3 medical centers in China. A total of 203 patients were enrolled who received 2 passes of EUS-FNA with 22-G needles. If the first pass underwent dry suction, the second pass was wet suction. Otherwise, the order of suction technique is opposite. Diagnostic accuracy, sample quality (including cellularity and blood contamination), and sample quantity (including specimen adequacy, the maximum intact specimen length, and the total specimen length) were compared between wet-suction and dry-suction techniques.

Results:

The patients included 143 pancreatic lesions and 60 nonpancreatic lesions. Compared with the dry suction technique, the wet suction technique yielded a significantly higher diagnostic accuracy (85.22% vs. 72.41%, P=0.002), better specimen adequacy score and cellularity score (P<0.0001), and lower blood contamination score (P<0.0001). In the subgroup analysis, wet suction provided significantly higher diagnostic accuracy in pancreatic cancer without chronic pancreatitis (P<0.05), and better cellularity score and specimen adequacy score, lower blood contamination score, and longer maximum intact specimen length and total specimen length in various lesions than that in dry suction.

Conclusions:

The wet suction technique resulted in significantly higher diagnostic accuracy in pancreatic cancer without chronic pancreatitis, and better cellularity and histologic specimen in most of solid lesions.
Adherence to Surveillance Endoscopies Posteradication of Barrett’s Esophagus With High-grade Dysplasia or Carcinoma In Situ
Authors: Um Phoebe S. , Chan Megan Q. , Hinton Alice , Haisley Kelly , Perry Kyle A. , Balasubramanian Gokulakrishnan
Published: April 2022

Goals:

We aimed to evaluate factors associated with patient adherence to recommended surveillance guidelines during the first 3 years after endoscopic eradication of Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or T1a carcinoma in situ (CIS) and the relationship between adherence and detection of recurrence.

Background:

While surveillance endoscopies after treatment of BE with HGD or T1a CIS are an important component of therapy, it is unclear whether these high-risk patients are adhering to recommended surveillance guidelines.

Materials and Methods:

A total of 123 BE patients who underwent radiofrequency ablation±endoscopic mucosal resection for biopsy-proven HGD, or CIS between January 2010 and November 2018 underwent retrospective review for adherence to surveillance guidelines, patient factors related to adherence, and recurrence of dysplasia or CIS at 12, 24, and 36 months.

Results:

Of 123 BE patients (89 HGD and 34 CIS), adherence during the first year following treatment was 26.97% for HGD patients and 41.18% for CIS patients, with increasing adherence rates in subsequent years. Patients who received 3 to 4 surveillance endoscopies in the first year posttreatment had significantly higher rates of recurrence detection than patients who received 0 to 2 surveillance endoscopies over this interval (P=0.01). No patient factors were found to impact adherence significantly.

Conclusions:

Adherence to recommended surveillance intervals after endoscopic treatment of BE with HGD or CIS is low, with poor adherence during the first year associated with decreased detection of recurrence. Future studies are needed to evaluate risk factors and develop a potential intervention for poor adherence in this high-risk population.
Associations Between Mobility, Food Insecurity, and Transactional Sex Among Women in Cohabitating Partnerships: An Analysis From 6 African Countries 2016–2017
Authors: Khalifa Aleya , Findley Sally , Gummerson Elizabeth , Mantell Joanne E. , Hakim Avi J. , Philip Neena M. , Ginindza Choice , Hassani Ahmed Saadani , Hong Steven Y. , Jalloh Mohamed F. , Kirungi Wilford L. , Maile Limpho , Mgomella George S. , Miller Leigh Ann , Minchella Peter , Mutenda Nicholus , Njau Prosper , Schwitters Amee , Ward Jennifer , Low Andrea
Published: April 2022

Background:

Mobile women are at risk of HIV infection in sub-Saharan Africa, although we lack evidence for HIV risk among women in mobile partnerships, especially in the context of household food insecurity, a growing concern in the region.

Setting:

Women aged 15–59 years with a cohabitating male partner who participated in population-based HIV impact assessment surveys in Eswatini, Lesotho, Namibia, Tanzania, Uganda, and Zambia.

Methods:

We evaluated the association between women's and their partner's mobility (being away from home for more than 1 month or staying elsewhere) and transactional sex (selling sex or receiving money or goods in exchange for sex). We examined associations for effect measure modification by food insecurity level in the household in the past month. We used survey-weighted logistic regression, pooled and by country, adjusting for individual, partner, and household-level variables.

Results:

Among women with a cohabitating male partner, 8.0% reported transactional sex, ranging from 2.7% in Lesotho to 13.4% in Uganda. Women's mobility [aOR 1.35 (95% CI: 1.08 to 1.68)], but not their partner's mobility [aOR 0.91 (0.74–1.12)], was associated with transactional sex. Food insecurity was associated with transactional sex independent of mobility [aOR 1.29 (1.10–1.52)]. Among those who were food insecure, mobility was not associated with increased odds of transactional sex.

Conclusion:

Food insecurity and women's mobility each increased the odds of transactional sex. Because transactional sex is associated with HIV risk, prevention programs can address the needs of mobile and food-insecure women, including those in cohabitating relationships.
Trans-border transfer of human biological materials in collaborative biobanking research: Perceptions and experiences of researchers in Uganda
Authors: Mwaka Erisa Sabakaki , Munabi Ian Guyton
Published: April 2022

Introduction

The study aimed to explore researchers’ perceptions and experiences on the transfer of human biological materials in international collaborative research.

Methods

This was a descriptive convergent parallel survey that randomly recruited 187 researchers involved in biobanking and/or genetics research. Data were collected using a self-administered tool that had both open and closed ended questions.

Results

Majority of respondents were male scientists (53.5%) with a mean research experience of 12.2 (SD 6.75) years. About 89% had ever worked in international collaborative research and 42% had ever participated in material transfer agreement (MTA) development. There were several areas of agreement in regard to the rights of local researchers and institution in collaborative biobanking research, and what details should be included in material transfer agreements. There was overwhelming support for collaborative partnership in biobanking research with 90.4% of researchers agreeing that local scientists should be involved in decisions making regarding the future use of samples. A majority (85.6%) opined that there should be fair sharing of research benefits with local researchers and populations or country from which the human biological materials were taken. Researchers felt that most MTAs tend to favour international collaborators. Several trust issues in the MTA development and implementation process were also highlighted and these included: lack of transparency and dishonesty of receiving scientists; lack of mechanisms to monitor the use of exported samples; ownership and intellectual property disputes; exploitation and inequitable sharing of research benefits; and authorship challenges. Several researchers seemed not to be conversant with the guidance provided by the Ugandan national ethics guidelines on the cross-border exchange of human biological specimens.

Conclusion

Local researchers had a positive attitude towards the export of human biological materials in collaborative research. However, there were several governance and trust concerns. There is a need for collaborative partnership in biobanking research.
Deep learning-based prognosis models accurately predict the time to delivery among preeclampsia patients using health records at the time of diagnosis
Authors: Yang Xiaotong , Ballard Hailey K , Mahadevan Aditya D , Xu Ke , Garmire David G , Langen Elizabeth S , Lemas Dominick J , Garmire Lana X
Published: April 2022

Background

Preeclampsia (PE) is one of the leading factors in maternal and perinatal mortality and morbidity worldwide with no known cure. Delivery timing is key to balancing maternal and fetal risk in pregnancies complicated by PE. Delivery timing of PE patients is traditionally determined by closely monitoring over a prolonged time. We developed and externally validated a deep learning models that can predict the time to delivery of PE patients, based on electronic health records (EHR) data by the time of the initial diagnosis, in the hope of reducing the need for close monitoring.

Method

Using the deep-learning survival model (Cox-nnet), we constructed time-to-delivery prediction models for all PE patients and early-onset preeclampsia (EOPE) patients. The discovery cohort consisted of 1,533 PE cases, including 374 EOPE, that were delivered at the University of Michigan Health System (UM) between 2015 and 2021. The validation cohort contained 2,172 PE cases (547 EOPE) from the University of Florida Health System (UF) in the same time period. We built clinically informative baseline models from 45 pre-diagnosis clinical variables that include demographics, medical history, comorbidity, PE severity, and initial diagnosis gestational age features. We also built full models from 60 clinical variables that include additional 15 lab tests and vital signs features around the time of diagnosis.

Results

The 7-feature baseline models on all PE patients reached C-indices of 0.74 and 0.73 on UM hold-out testing and UF validation dataset respectively, whereas the 12-feature full model had improved C-indices of 0.79 and 0.74 on the same datasets. For the more urgent EOPE cases, the 6-feature baseline model achieved C-indices of 0.68 and 0.63, and its 13-feature full model counterpart reached C-indices of 0.76 and 0.67 in the same datasets.

Conclusions

We successfully developed and externally validated an accurate deep-learning model for time-to-delivery prediction among PE patients at the time of diagnosis, which helps to prepare clinicians and patients for expected deliveries.
Automated method to extract and purify RNA from wastewater enables more sensitive detection of SARS-CoV-2 markers in community sewersheds
Authors: West Nicholas W. , Vasquez Adrian A. , Bahmani Azadeh , Khan Mohammed , Hartrick James , Turner Carrie L. , Shuster William , Ram Jeffrey L.
Published: April 2022

Wastewater based epidemiology (WBE) has emerged as a strategy to identify, locate, and manage outbreaks of COVID19, and thereby possibly prevent surges in cases, which overwhelm local to global health care networks. The WBE process is based on assaying municipal wastewater for molecular markers of the SARS-CoV-2 virus. The standard process for sampling municipal wastewater is both time-consuming and requires the handling of large quantities of wastewater, which negatively affect throughput and timely reporting, and can increase safety risks. We report on a method to assay multiple sub-samples of a bulk wastewater sample. We document the effectiveness of this new approach by way of comparison of technologies for automating RNA purification from wastewater samples. We compared processes using the Perkin-Elmer Chemagic™ 360 to a PEG/NaCl/Qiagen protocol that is used for detection of N1 and N2 SARS-CoV-2 markers by the majority of 19 pandemic wastewater testing labs in the State of Michigan. Specifically, we found that the Chemagic™ 360 lowered handling time, decreased the amount of wastewater required by 10-fold, increased the amount of RNA isolated per µl of final elution product by approximately five-fold, and had no deleterious effect on subsequent ddPCR analysis. Moreover, for detection of markers on the borderline of detectability, we found that use of the Chemagic™ 360 enabled the detection of viral markers in a significant number of samples for which the result with the PEG/NaCl/Qiagen method was below the level of detectability. This improvement in detectability of the viral markers might be particularly important for early warning to public health authorities at the beginning of an outbreak.
Reactivating ordinal position information from auditory sequence memory in human brains
Authors: Fan Ying , Luo Huan
Published: April 2022

Retaining a sequence of events in their order is a core ability of many cognitive functions, such as speech recognition, movement control, and episodic memory. Although content representations have been widely studied in working memory (WM), little is known about how ordinal position information of an auditory sequence is retained in the human brain as well as its coding characteristics. In fact, there is still a lack of an efficient approach to directly access the stored ordinal position code, since the neural activities enter a relatively ‘activity-silent’ WM state during WM retention. Here participants performed an auditory sequence WM task with their brain activities recorded using electroencephalography (EEG). We developed new triggering events that could successfully reactivate neural representations of ordinal position from the ‘activity-silent’ retention stage. Importantly, the rank reactivation is further related to recognition behavior, confirming its indexing of WM storage. Furthermore, the ordinal position code displays an intriguing ‘stable-dynamic’ format, i.e., undergoing the same dynamic neutral trajectory during both encoding and retention (whenever reactivated). Overall, our results provide an effective approach to access the behaviorally-relevant ordinal position information in auditory sequence WM and reveal its new temporal characteristics.
Population modeling with machine learning can enhance measures of mental health - Open-Data Replication
Authors: Easley Ty , Chen Ruiqi , Hannon Kayla , Dutt Rosie , Bijsterbosch Janine
Published: April 2022

Efforts to predict trait phenotypes based on functional MRI data from large cohorts have been hampered by low prediction accuracy and/or small effect sizes. Although these findings are highly replicable, the small effect sizes are somewhat surprising given the presumed brain basis of phenotypic traits such as neuroticism and fluid intelligence. We aim to replicate previous work and additionally test multiple data manipulations that may improve prediction accuracy by addressing data pollution challenges. Specifically, we added additional fMRI features, averaged the target phenotype across multiple measurements to obtain more accurate estimates of the underlying trait, balanced the target phenotype’s distribution through undersampling of majority scores, and identified data-driven subtypes to investigate the impact of between-participant heterogeneity. Our results replicated prior results from Dadi et a (2021) in a larger sample. Each data manipulation further led to small but consistent improvements in prediction accuracy, which were largely additive when combining multiple data manipulations. Combining data manipulations (i.e., extended fMRI features, averaged target phenotype, balanced target phenotype distribution) led to a three-fold increase in prediction accuracy for fluid intelligence compared to prior work. These findings highlight the benefit of several relatively easy and low-cost data manipulations, which may positively impact future work.
Changing patterns of SARS-CoV-2 infection through Delta and Omicron waves by vaccination status, previous infection and neighbourhood deprivation: A cohort analysis of 2.7M people
Authors: Green Mark A. , Hungerford Daniel J. , Hughes David M. , Garcia-Fiñana Marta , Turtle Lance , Cheyne Christopher , Ashton Matthew , Leeming Gary , Semple Malcolm G. , Singleton Alex , Buchan Iain
Published: April 2022

Objective

To examine if SARS-CoV-2 infections vary by vaccination status, if an individual had previously tested positive and by neighbourhood socioeconomic deprivation across the Delta and Omicron epidemic waves of SARS-CoV-2.

Design

Cohort study using electronic health records

Setting

Cheshire and Merseyside, England (3rd June 2021 to 1st March 2022)

Participants

2.7M residents

Main Outcome measure

Registered positive test for SARS-CoV-2

Results

Social inequalities in registered positive tests were dynamic during the study. Originally higher SARS-CoV-2 rates in the most socioeconomically deprived neighbourhoods changed to being higher in the least deprived neighbourhoods from the 1st September 2021. While the introduction of Omicron initially reset inequalities, they continued to be dynamic and inconsistent. Individuals who were fully vaccinated (two doses) were associated with fewer registered positive tests (e.g., between 1st September and 27th November 2021: (i) individuals engaged in testing – Hazards Ratio (HR) = 0.48, 95% Confidence Intervals (CIs) = 0.47-0.50; (ii) individuals engaged with healthcare - HR = 0.34, 95% CIs = 0.33-0.34). Individuals with a previous registered positive test were also less likely to have a registered positive test (e.g., between 1st September and 27th November 2021: (i) individuals engaged in testing - HR = 0.16, 95% CIs = 0.15-0.18; (ii) individuals engaged with healthcare - HR = 0.14, 95% CIs = 0.13-0.16). However, Omicron is disrupting these associations due to immune escape resulting in smaller effect sizes for both measures.

Conclusions

Changing patterns of SARS-CoV-2 infections during the Delta and Omicron waves reveals a dynamic pandemic that continues to affect diverse communities in sometimes unexpected ways.
Extracting multiple surfaces from 3D microscopy images in complex biological tissues with the Zellige software tool
Authors: Trébeau Céline , de Monvel Jacques Boutet , Altay Gizem , Tinevez Jean-Yves , Etournay Raphaël
Published: April 2022

Efficient tools allowing the extraction of 2D surfaces from 3D-microscopy data are essential for studies aiming to decipher the complex cellular choreography through which epithelium morphogenesis takes place during development. Most existing methods allow for the extraction of a single and smooth manifold of sufficiently high signal intensity and contrast, and usually fail when the surface of interest has a rough topography or when its localization is hampered by other surrounding structures of higher contrast. Multiple surface segmentation entails laborious manual annotations of the various surfaces separately. As automating this task is critical in studies involving tissue-tissue or tissue-matrix interaction, we developed the Zellige software, which allows the extraction of a non-prescribed number of surfaces of varying inclination, contrast, and texture from a 3D image. The tool requires the adjustment of a small set of control parameters, for which we provide an intuitive interface implemented as a Fiji plugin. As a proof of principle of the versatility of Zellige, we demonstrate its performance and robustness on synthetic images and on four different types of biological samples, covering a wide range of biological contexts.
Time series analysis of SARS-CoV-2 genomes and correlations among highly prevalent mutations
Authors: Periwal Neha , Rathod Shravan B. , Sarma Sankritya , Singh Gundeep , Jain Avantika , Barnwal Ravi P. , Srivastava Kinsukh R. , Kaur Baljeet , Arora Pooja , Sood Vikas
Published: April 2022

The efforts of the scientific community to tame the recent SARS-CoV-2 pandemic seems to have been diluted by the emergence of new viral strains. Therefore, it becomes imperative to study and understand the effect of mutations on viral evolution, fitness and pathogenesis. In this regard, we performed a time-series analysis on 59541 SARS-CoV-2 genomic sequences from around the world. These 59541 genomes were grouped according to the months (January 2020-March 2021) based on the collection date. Meta-analysis of this data led us to identify highly significant mutations in viral genomes. Correlation and Hierarchical Clustering of the highly significant mutations led us to the identification of sixteen mutation pairs that were correlated with each other and were present in >30% of the genomes under study. Among these mutation pairs, some of the mutations have been shown to contribute towards the viral replication and fitness suggesting the possible role of other unexplored mutations in viral evolution and pathogenesis. Additionally, we employed various computational tools to investigate the effects of T85I, P323L, and Q57H mutations in Non-structural protein 2 (Nsp2), RNA-dependent RNA polymerase (RdRp) and Open reading frame 3a (ORF3a) respectively. Results show that T85I in Nsp2 and Q57H in ORF3a mutations are deleterious and destabilize the parent protein whereas P323L in RdRp is neutral and has a stabilizing effect. The normalized linear mutual information (nLMI) calculations revealed the significant residue correlation in Nsp2 and ORF3a in contrast to reduce correlation in RdRp protein.
Lichen speciation is sparked by a substrate requirement shift and reproduction mode differentiation
Authors: Kantelinen Annina , Printzen Christian , Poczai Péter , Myllys Leena
Published: April 2022

We show that obligate lignicoles in lichenizedMicareaare predominately asexual whereas most facultative lignicoles reproduce sexually. Our 3 loci phylogenetic analyses (ITS, mtSSU,Mcm7) together with ancestral state reconstruction show that the shift in reproduction mode has evolved independently several times within the group and that facultative and obligate lignicoles are sister species. The analyses support the assumption that the ancestor of these species was a facultative lignicole. We hypotezise that a shift in substrate requirement from bark to wood leads to differentiation in reproduction mode and becomes a driver of speciation. This is the first example of lichenized fungi where reproduction mode is linked to substrate requirement. This is also the first example where such a linkage is demonstrated to spark lichen speciation. Our main hypothesis is that obligate species on dead wood need to colonize new suitable substrata relatively fast and asexual reproduction is more effective a strategy for successful colonization. Our main hypothesis for explaining the discovered phenomenon involves the species’ life cycle: species on decaying wood face a significant challenge because the ecological properties of their substratum change relatively fast. When this happens, species need to colonize new suitable substrata. This may set a time limit, where asexual reproduction is a faster and more effective strategy for successful colonization.
Potential impact of TE-derived sRNA on gene regulation in the grassBrachypodium distachyon
Authors: Wyler Michele , Keller Bettina , Roulin Anne C
Published: April 2022

In plants, the transcriptional and post-transcriptional repression of TEs involved the production of small interfering RNAs (siRNAs) that guide thede novomethylation and transcriptional silencing of TEs. Because siRNAs act via sequence complementarity, they indiscriminately target TEs and possible non-TE transcripts. TEs and their derived siRNAs might thus provide a reservoir for long-distance gene regulation. To test this hypothesis, we infectedBrachypodium distachyonwithMangnaporte oryzae, the agent of Rice Blast. The infection caused the differential expression of multiple TE copies as well as a global change in gene expression. By sequencing the small RNA fraction, we identified TE-derived sRNA that are identical in sequence to motifs contained in the UTR region of differentially expressed genes. Our study opens new avenues of research to further investigate to what extent TEs may serve as a source for in trans gene regulation.
Obstacles to inferring mechanistic similarity using Representational Similarity Analysis
Authors: Dujmović Marin , Bowers Jeffrey S , Adolfi Federico , Malhotra Gaurav
Published: April 2022

Representational Similarity Analysis (RSA) is an innovative approach used to compare neural representations across individuals, species and computational models. Despite its popularity within neuroscience, psychology and artificial intelligence, this approach has led to difficult-to-reconcile and contradictory findings, particularly when comparing primate visual representations with deep neural networks (DNNs). Here, we demonstrate how such contradictory findings could arise due to incorrect inferences about mechanism when comparing complex systems processing high-dimensional stimuli. In a series of studies comparing computational models, primate cortex and human cortex we find two problematic phenomena: a “mimic effect”, where confounds in stimuli can lead to high RSA-scores between provably dissimilar systems, and a “modulation effect”, where RSA- scores become dependent on stimuli used for testing. Since our results bear on a number of influential findings, we provide recommendations to avoid these pitfalls and sketch a way forward to a more solid science of representation in cognitive systems.
Reduced injury risk links sociality to survival in a group-living primate
Authors: Pavez-Fox Melissa A. , Kimock Clare M. , Rivera-Barreto Nahiri , Negron-Del Valle Josue E. , Phillips Daniel , Ruiz-Lambides Angelina , Snyder-Mackler Noah , Higham James P. , Siracusa Erin R. , Brent Lauren J.N.
Published: April 2022

Affiliative social relationships and high social status predict longer lifespans in many mammal species, including humans. Yet, the mechanisms by which these components of sociality influence survival are still largely unknown. Using 10 years of data and over 1000 recorded injuries from a free-ranging population of rhesus macaques (Macaca mulatta), we investigated two possible mechanisms that could underpin the relationship between sociality and survival: sociality (1) reduces injury risk; and/or (2) increases the probability of survival after an injury. We found that sociality can affect an individual’s survival by influencing their risk of injury, but had no effect on the probability of injured individuals dying. Individuals with more affiliative partners experienced fewer injuries compared to less socially integrated. Social status was also associated with lower risk of injury, particularly for older high-ranking individuals. These results represent the first demonstration of a link between social integration and fatal injury risk in a group-living species, and are the first to link social status, injury risk and survival outside of humans. Collectively, our results offer insights into a mechanism that can mediate the well-known benefits of sociality on an individual’s fitness.
Membrane interactions of mitochondrial lipid transfer proteins
Authors: Sadeqi Fereshteh , Stroh Kai , Vache Marian , Riedel Dietmar , Janshoff Andreas , Risselada Herre Jelger , Meinecke Michael
Published: April 2022

The mitochondrial inner membrane is an integral part of the cellular lipid biosynthesis network. Intramitochondrial lipid transfer shuttles specific lipid species between the two mitochondrial membranes. This pathway is facilitated by designated protein complexes in the intermembrane space. A hetero-dimeric complex of Ups1 and Mdm35 has been identified in yeast to transfer phosphatidic acid from the outer to the inner membrane. Here, we define pH and lipid charge dependency of Ups1 membrane interaction. We show that Ups1 interacts with membranes in a membrane curvature dependent manner. Ups1 predominantly binds to membrane domains of positive curvature. Desorption of phosphatidic acid from positively curved membranes is energetically favorable over flat or negatively curved membranes. Hence, our results demonstrate that Ups1 specifically binds to membrane regions where extraction and insertion of lipids is enhanced.
QuasiFlow: a bioinformatic tool for genetic variability analysis from next generation sequencing data
Authors: Seoane Pedro , Díaz-Martínez Luis , Viguera Enrique , Claros M. Gonzalo , Grande-Pérez Ana
Published: April 2022

Populations of RNA and ssDNA viruses within their hosts contain a heterogeneous collection of variant genomes known as quasispecies. Large variability in mitochondrial DNA has also been found within the same organism, drawing an interesting parallel between the two situations. The advent of next-generation sequencing technologies facilitated studying genetic variation, but many open-source bioinformatic tools have to be combined in a non-trivial approach. Here it is presented QuasiFlow, a workflow based on well-stablished software that extracts reliable mutations and recombinations, even at low frequencies (~10-4), provided that at least 250 million nucleotides are analysed. Accurate prediction of mutations and recombinations has been demonstrated with synthetic reads and with in vitro rolling-circle amplification of a plant geminivirus. An in-depth analysis of viral quasispecies was performed and QuasiFlow revealed the coexistence in the plant of three virus genomes and distinct recombinations between some of them. Human mitochondrial variants were also investigated and high level of heteroplasmy (75%) was confirmed, and the relation between low-frequency heteroplasmy (0.1- 0.2%) and some human diseases, regardless of sex, was established. Hence, we propose that QuasiFlow may find use with known and emerging viruses to reveal evolutionary jumps and co-infections, with mitochondrial DNA to detect relevant heteroplasmy would otherwise be elusive, or even in other population studies such as those considering single cell sequencing.
Efficient Permutation-based Genome-wide Association Studies for Normal and Skewed Phenotypic Distributions
Authors: John Maura , Ankenbrand Markus J , Artmann Carolin , Freudenthal Jan A , Korte Arthur , Grimm Dominik G
Published: April 2022

Motivation

Genome-wide Association Studies (GWAS) are an integral tool for studying the architecture of complex genotype and phenotype relationships. Linear Mixed Models (LMMs) are commonly used to detect associations between genetic markers and the trait of interest, while at the same time allowing to account for population structure and cryptic relatedness. Assumptions of LMMs include a normal distribution of the residuals and that the genetic markers are independent and identically distributed - both assumptions are often violated in real data. Permutation-based methods can help to overcome some of these limitations and provide more realistic thresholds for the discovery of true associations. Still, in practice they are rarely implemented due to its high computational complexity.

Results

We propose permGWAS, an efficient linear mixed model reformulation based on 4D-tensors that can provide permutation-based significance thresholds. We show that our method outperforms current state-of-the-art LMMs with respect to runtime and that a permutation-based threshold has a lower false discovery rate for skewed phenotypes compared to the commonly used Bonferroni threshold. Furthermore, using permGWAS we re-analysed more than 500 Arabidopsis thaliana phenotypes with 100 permutations each in less than eight days on a single GPU. Our re-analyses suggest that applying a permutation-based threshold can improve and refine the interpretation of GWAS results.

Availability

permGWAS is open-source and publicly available on GitHub for download: https://github.com/grimmlab/permGWAS.
Nucleoporins facilitate ORC loading onto chromatin
Authors: Richards Logan , Lord Christopher L. , Benton Mary Lauren , Capra John A. , Nordman Jared T.
Published: April 2022

The origin recognition complex (ORC) binds throughout the genome to initiate DNA replication. In metazoans, it is still unclear how ORC is targeted to specific loci to facilitate helicase loading and replication initiation. Here, we performed immunoprecipitations coupled with mass spectrometry for ORC2 in Drosophila embryos. Surprisingly, we found that ORC2 associates with multiple subunits of the Nup107-160 subcomplex of the nuclear pore. Bioinformatic analysis revealed that, relative to all modENCODE factors, nucleoporins are among the most enriched factors at ORC2 binding sites. Critically, depletion of the nucleoporin Elys, a member of the Nup107-160 complex, results in decreased ORC2 loading onto chromatin. Depleting Elys also sensitized cells to replication fork stalling, which could reflect a defect in establishing dormant replication origins. Our work reveals a new connection between ORC, replication initiation and nucleoporins, highlighting a previously unrecognized function of nucleoporins in metazoan replication initiation.
Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages
Authors: Ai Jingwen , Wang Xun , He Xinyi , Zhao Xiaoyu , Zhang Yi , Jiang Yuchao , Li Minghui , Cui Yuchen , Chen Yanjia , Qiao Rui , Li Lin , Yang Lulu , Li Yi , Hu Zixin , Zhang Wenhong , Wang Pengfei
Published: April 2022

The SARS-CoV-2 Omicron variant has been partitioned into four sub-lineages designated BA.1, BA.1.1, BA.2 and BA.3, with BA.2 becoming dominant worldwide recently by outcompeting BA.1 and BA.1.1. We and others have reported the striking antibody evasion of BA.1 and BA.2, but side-by-side comparison of susceptibility of all the major Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are urgently needed. Using VSV-based pseudovirus, we found that sera from individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV) showed very weak to no neutralization activity, while a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) markedly improved the neutralization titers against all Omicron variants. The comparison between sub-lineages indicated that BA.1.1, BA.2 and BA.3 had comparable or even greater antibody resistance than BA.1. We further evaluated the neutralization profile of a panel of 20 mAbs, including 10 already authorized or approved, against these Omicron sub-lineages as well as viruses with different Omicron spike single or combined mutations. Most mAbs lost their neutralizing activity completely or substantially, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, reflecting their antigenic difference. Taken together, our results suggest all four Omicron sub-lineages threaten the efficacies of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters to combat the emerging SARS-CoV-2 variants.
Topography of histone H3–H4 interaction with the Hat1–Hat2 acetyltransferase complex
Authors: Yue Ye , Yang Wen-Si , Zhang Lin , Liu Chao-Pei , Xu Rui-Ming
Published: April 2022

Chaperones influence histone conformation and intermolecular interaction in multiprotein complexes, and the structures obtained with full-length histones often provide more accurate and comprehensive views. Here, our structure of the Hat1–Hat2 acetyltransferase complex bound to Asf1–H3–H4 shows that the core domains of H3 and H4 are involved in binding Hat1 and Hat2, and the N-terminal tail of H3 makes extensive interaction with Hat2. These findings expand the knowledge about histone–protein interaction and implicate a function of Hat2/RbAp46/48, which is a versatile histone chaperone found in many chromatin-associated complexes, in the passing of histones between chaperones.
Impact of green human resource practices on hotel environmental performance: the moderating effect of environmental knowledge and individual green values
Authors: Raza Syed Ali , Khan Komal Akram
Published: April 2022

Purpose

Green management initiatives are an influential factor for forward-thinking corporations across the globe. Human resource (HR) practitioners find incorporating sustainable development into HR practices a significant challenge, but green initiatives enhance environmental quality. This study aims to analyze the impact of green human resources management (GHRM) practices on hotel environmental performance (HEP) by incorporating environmental knowledge (EK) and individual green values (IGV) as a moderator.

Design/methodology/approach

The software Smart PLS has been used for data analysis, and partial least square-structural equation modeling has been used to assess measurement and structural models. Data was gathered from 329 white-collar employees of Pakistan’s guest service hotels.

Findings

The results reveal that GHRM practices positively correlate with employees’ affective commitment (EAC) and eco-friendly behavior. Also, employees’ eco-friendly behavior increases HEP, but EAC shows an insignificant association. Moreover, EK does not strengthen the relationship between GHRM practices and EAC and eco-friendly behavior. However, IGV strengthen the relationship between affective commitment and HEP.

Practical implications

The research suggests that management should embrace GHRM practices for better environmental performance. Hotels should ensure that all GHRM attributes, such as green recruitment, training and compensation, are rightly executed. They can help acquire and retain committed and eco-friendly employees whose environmental values and objectives are compatible with the organization.

Originality/value

It will provide insight into the role of the GHRM in fostering EAC and eco-friendly behavior that, in turn, influence environmental performance. Also, the theory of social identity has been incorporated to inspect employees’ behavior along with the moderating role of EK and IGV. It is crucial to understand two essential aspects in a developing country like Pakistan so that the hospitality sector can implement them efficiently in the future: how hotels protect the environment through their green practices and whether employees of a developing country depict eco-friendly behavior and affective commitment on the basis of GHRM.