bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA circMRPS35 regulates progression and autophagy in osteosarcoma cells by recruiting KAT6B to govern FOXO3
Authors: Jiang Chunshan , Jiang Zhe , Zhang Xuewu
Published: May 2022

Osteosarcoma serves as frequently occurred bone malignancy that displays low survival rate and high incidence of metastasis. Circular RNAs (circRNAs) have been reported as the crucial molecules in osteosarcoma development. However, the effect of circRNA circMRPS35 on osteosarcoma remains unclear. Here, we aimed to explore the function of circMRPS35 in the regulation of autophagy and progression of osteosarcoma. The colony formation numbers and Edu-positive osteosarcoma cells were repressed by the overexpression of circMRPS35. Meanwhile, the overexpression of circMRPS35 increased the apoptosis rate of osteosarcoma cells. The expression levels of autophagy markers, including LC3 and Beclin1, were enhanced by the overexpression of circMRPS35 in osteosarcoma cells. Mechanically, the depletion of circMRPS35 reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) on forkhead box O3 (FOXO3) promoter in osteosarcoma cells. The interaction of circMRPS35 and KAT6B was identified. The knockdown of KAT6B reduced the enrichment of H3K23ac on FOXO3 promoter in osteosarcoma cells. The depletion of circMRPS35 repressed the expression of FOXO3 in the MG63 and MNNG/HOS cells, whereas the overexpression of KAT6B reversed the effect. Significantly, KAT6B promotes apoptosis and autophagy of osteosarcoma cells. The overexpression of circMRPS35 induced the apoptosis and autophagy of osteosarcoma cells, in which the depletion of KAT6B or FOXO3 reversed the effect. The overexpression of circMRPS35 inhibited the tumor growth in vivo, whereas the depletion of KAT6B could reverse the effect in the mice. Therefore, we concluded that circRNA circMRPS35 repressed progression and induced autophagy of osteosarcoma cells.
Multigenerational effects of paternal spatial training are lasting in the F1 and F2 male offspring
Authors: Riyahi Javad , Abdoli Behrouz , Gelfo Francesca , Petrosini Laura , Khatami Leila , Meftahi Gholam Hossein , Haghparast Abbas
Published: May 2022

Recent studies on intergenerational transmission of learning and memory performances demonstrated that parental spatial training before fertilization could facilitate learning and memory in the offspring, but many questions remain unclarified. Essential issues regarding whether and how long the effects of parental training in a task can last in several generations, and whether learning a task repeated in the successive generations can enhance a load of multigenerational effects. In the present study, the spatial performances of F1 and F2 generations of male offspring of fathers or grandfathers spatially trained in the Morris Water Maze were evaluated and compared with the performance of a control sample matched for age and sex. Further, to investigate the memory process in F1 and F2 male offspring, brain-derived neurotrophic factor (BDNF), p-ERK1/2 and acetylated histone 3 lysine 14 (H3K14) expression levels in the hippocampus were analyzed. The findings showed that paternal training reduced escape latencies and increased time spent in the target quadrant by F1 and F2 male offspring. Besides, paternal spatial training repeated in two generations did not enhance the beneficial effects on offspring’s spatial performances. These findings were supported by neurobiologic data showing that paternal training increased BDNF and p-ERK1/2 in the hippocampus of F1 and F2 male offspring. Furthermore, the hippocampal level of acetylated H3K14 increased in the offspring of spatially trained fathers, reinforcing the hypothesis that the augmented histone acetylation might play an essential role in the inheritance of spatial competence.
A Rare Anatomical Finding of Undescribed Accessory Palmaris Longus in the Distal Forearm: A Case Report
Authors: Allahham Salim , Alyazji Zaki T. N. , Aljassem Ghanem , Sada Ruba , Wani Iqbal Rasool
Published: May 2022

Upper limb muscle anomalies and their clinical implications have been described frequently in the literature reviews. In this article, we are presenting a case of aberrant forearm muscle that had not been described before, and could be considered as a palmaris longus muscle variation. A 24-year-old man presented to the emergency department, Hamad General Hospital, Doha, Qatar, with right forearm laceration with multiple cut structures for which he was admitted for exploration and repair. Intraoperatively, flexor digitorum superficialis of the third, fourth, and fifth digits, flexor carpi radialis, and palmaris longus were injured‚ and all of them were repaired. We noticed an aberrant muscle—which was also injured—that originated from the distal third of the radius on its medial aspect to insert into the palmar fascia; pulling this muscle’s tendon resulted in tightening of palmar fascia‚ same as the palmaris longus. Along with the importance of deep knowledge of typical human anatomy, hand surgeons must be aware that an aberration from normal anatomy might be anticipated, to provide the best care to our patients.
EFFECTS OF ECTOPIC INNER FOVEAL LAYERS ON FOVEAL CONFIGURATION AND VISUAL FUNCTION AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY
Authors: Yang Xiaohan , Wang Zengyi , Yu Yanping , Mo Bin , Zhang Ke , Wu XiJin , Liu Lingzi , Wang Xinbo , Qi Biying , Liu Wu
Published: May 2022

Purpose:

To investigate the effects of ectopic inner foveal layers (EIFLs) on foveal configuration recovery and visual acuity after idiopathic epiretinal membrane removal and analyze the relationship of foveal configuration recovery between 1-month and long-term postoperatively.

Methods:

This retrospective study included 216 consecutive eyes with idiopathic epiretinal membrane that underwent vitrectomy surgery. A comprehensive ophthalmic examination was performed for all patients before and 1, 4, 10, and 24 months after surgery. We observed the postoperative anatomical and functional recovery of eyes with and without EIFLs and analyzed the association between short-term and long-term anatomical recovery.

Results:

The presence of EIFL was associated with severe preoperative visual damage (P < 0.001) and was considered as a negative factor for postoperative foveal depression recovery (P < 0.001). No significant difference was found in postoperative best-corrected visual acuity between the eyes with and without EIFLs (P = 0.442). For eyes with Stage II epiretinal membranes, 17.6% developed EIFLs postoperatively, which did not affect the final best-corrected visual acuity. Overall, 24.5% of epiretinal membranes restored the foveal configurations at 1 month postoperatively, and 14.7% continued recovering during the follow-up. Foveal structure recovery in eyes with EIFLs was associated with earlier stage, fewer microcystic macular edema, complete interdigitation zone layer, and a thinner central foveal thickness (all P < 0.05) at 1 month postoperatively.

Conclusion:

The EIFL is associated with severe preoperative visual damage and is a negative factor for postoperative anatomical recovery, but it is a minor factor for postoperative visual acuity. We also found an association of foveal configuration recovery between 1 month and long-term after surgery.
IMPACT OF COVID-19 PANDEMIC LOCKDOWNS ON VISUAL ACUITY OF PATIENTS WITH NEOVASCULAR AMD
Authors: Shor Reut , Segal Ori , Mimouni Michael , Greenbaum Eran , Zur Dinah , Trivizki Omer , Schwartz Shulamit , Loewenstein Anat , Goldstein Michaella , Rabina Gilad
Published: May 2022

Purpose:

Evaluating the impact of delayed care, secondary to coronavirus disease 2019 (COVID-19) pandemic lockdowns, on visual acuity in previously treated neovascular age-related macular degeneration (nAMD) patients.

Methods:

This was a multicenter, retrospective, study of patients with nAMD previously treated with anti-VEGF injections who were followed up during 2019 (pre–COVID-19) and compared with patients with nAMD during 2020 (COVID-19).

Results:

A total of 1,192 patients with nAMD with a mean age of 81.5 years met the inclusion criteria. Of these, 850 patients were assessed in 2019 (pre–COVID-19) and 630 patients were assessed in 2020 (COVID-19). Three hundred eight patients were assessed through both 2019 and 2020 and thus were included in both cohorts. There was no significant difference between 2020 and 2019 in baseline and change in best-corrected visual acuity (BCVA;P= 0.342 andP= 0.911, respectively). The mean number of anti-VEGF injections was significantly lower (5.55 vs. 6.13,P< 0.01), with constant lower ratio of injections per patient in the COVID-19 period. Baseline BCVA (0.859,P< 0.01), number of injections (−0.006,P= 0.01), and age (0.003,P< 0.01) were predictors of final BCVA.

Conclusion:

In patients with nAMD, delayed care secondary to COVID-19 pandemic lockdowns has no statistically significant impact on BCVA. Best-corrected visual acuity, older age, and lower number of yearly anti-VEGF injections are predictors for decrease BCVA.
HENLE FIBER LAYER MAPPING WITH DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY
Authors: Kesim Cem , Bektas Sevval Nur , Kulali Zeynep , Yildiz Erdost , Ersoz M. Giray , Sahin Afsun , Gunduz-Demir Cigdem , Hasanreisoglu Murat
Published: May 2022

Purpose:

To perform a macular volumetric and topographic analysis of Henle fiber layer (HFL) from retinal scans acquired by directional optical coherence tomography.

Methods:

Thirty healthy eyes of 17 subjects were imaged using the Heidelberg spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany) with varied horizontal and vertical pupil entry. Manual segmentation of HFL was performed from retinal sections of horizontally and vertically tilted optical coherence tomography images acquired within macular 20 × 20° area. Total HFL volume, mean HFL thickness, and HFL coverage area within Early Treatment for Diabetic Retinopathy Study grid were calculated from mapped images.

Results:

Henle fiber layer of 30 eyes were imaged, segmented and mapped. The mean total HFL volume was 0.74 ± 0.08 mm3 with 0.16 ± 0.02 mm3, 0.18 ± 0.03 mm3, 0.17 ± 0.02 mm3, and 0.19 ± 0.03 mm3 for superior, temporal, inferior, and nasal quadrants, respectively. The mean HFL thickness was 26.5 ± 2.9 µm. Central 1-mm macular zone had the highest mean HFL thickness with 51.0 ± 7.6 µm. The HFL coverage that have thickness equal or above to the mean value had a mean 10.771 ± 0.574 mm2 of surface area.

Conclusion:

Henle fiber layer mapping is a promising tool for structural analysis of HFL. Identifying a normative data of HFL morphology will allow further studies to investigate HFL involvement in various ocular and systemic disorders.
Impact of Simulation on Undergraduate Student Outcomes
Authors: Thomas Christine M. , Barker Nancy
Published: May 2022

Background:

Clinical reasoning is a cognitive and metacognitive process that is essential for positive patient outcomes. Simulation experiences provide situations and reflection where students can build clinical reasoning.

Purpose:

This study examined the impact of a higher number of simulation experiences on undergraduate student outcomes.

Methods:

A retrospective comparison study examined differences between group grade point average, Assessment Technologies Institute (ATI) predictor, and National Council Licensure Examination (NCLEX) scores (P < .05). A sample of 395 students was included in data analysis.

Results:

No differences were noted in grade point average or NCLEX pass rates. However, students who completed a simulation elective had significantly higher ATI predictor scores. Cohen's d (0.39) approached a medium effect size.

Conclusions:

Incorporating higher levels of in-person simulation through creative delivery models can improve student outcomes. Simulations may enhance students' clinical reasoning skills.
Transitioning a Graduate Nursing Physical Examination Skills Lab to an Online Learning Modality
Authors: Barnes Emily R. , Vance Billie S.
Published: May 2022

Background:

Continued restrictions imposed on face-to-face learning related to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) pandemic resulted in a decision to permanently transition a graduate nursing education advanced assessment course from a hybrid to an online learning modality.

Purpose:

The purpose of this article is to describe the transition of the physical examination skills lab from face-to-face to online, compare advanced practice nursing student performance outcomes, and evaluate faculty satisfaction and student satisfaction and confidence in learning.

Methods:

A retrospective comparison design was used to evaluate student outcomes. Surveys were used to evaluate faculty satisfaction and student satisfaction and confidence.

Results:

Academic performance, including the psychomotor performance proficiency of advanced assessment skills, was comparable between the modalities. Students were satisfied with and confident in their learning of skills. Faculty support online delivery despite increased workload.

Conclusions:

Continued use of the online learning modality for teaching advanced physical examination skills is warranted.
Rotation Advancement Keystone Flap for Closure of Large Myelomeningocele Defects
Authors: Hifny Mahmoud A. , Hamdan Ali R. , Tayel Amr M. , El Khateeb Eslam El-Sayed , Yagi Shunjiro , Park Tae Hwan
Published: May 2022

Introduction

Myelomeningocele is the most common form of neural tube anomalies. Early reliable skin coverage should be achieved to reduce central nervous system infections. The keystone flaps are gaining popularity for myelomeningocele defect reconstruction. However, the use of a traditional keystone flap is limited in very wide or transversely oriented myleomeningocele defects with inadequate lateral tissue laxity. In this study, we present our successful experience using modified rotation advancement keystone flaps for closure of the transversely oriented myelomeningocele defects.

Patients and Methods

Between April 2019 and April 2020, the modified rotation advancement keystone flap was used for reconstruction of transversely oriented myelomeningocele defect in 7 patients (5 males and 2 females) with average age of 14 days. The localization of the lesions was lumbosacral in 5 patients and thoracolumbar in 2 patient. The average myelomeningocele defect width was 6.4 cm, whereas the average defect length was 5.7 cm. The following information was evaluated: the flap dimensions, operative time, and postoperative complications.

Results

All patients had uneventful operations, except for 1 case of superficial epidermolysis over flap tip, which settled with conservative wound management. Immediate venous congestion was detected in 2 patients that completely resolved. Otherwise, all wounds healed without any evidence of complications. The mean follow-up was 4 months.

Conclusions

Although the conventional keystone flap seems to have geometric constraints to close a transversally oriented myelomeningocele defect, the modified rotation advancement keystone flap serves as a superior alternative and effective option for closure transversally oriented defect.
An Evaluation of Racial Disparities in Online Marketing of Academic Plastic Surgery Practices
Authors: Moss Whitney D. , King Brody W. , Memmott Stanley , Pires Giovanna , Rosales Megan , Kwok Alvin , Tenzel Paul
Published: May 2022

Background

Racial disparities in plastic surgery limit health care accessibility and quality. The aim of this study is to determine if racial disparities exist within patient-targeted advertising materials on academic plastic surgery practice (APSP) Web sites and if disparities are more pronounced in specific categories within plastic surgery.

Methods

Throughout May 2021, 3 independent reviewers analyzed the Web sites for APSPs and identified all photos, videos, and graphics with visible skin. For each image, the Fitzpatrick skin tone scale was used to classify the skin tone as “White” (I–III) or “non-White” (IV–VI). The images were further categorized based on the type of procedure depicted. Comparisons were made to publish US census data using χ2 tests and linear mixed effects models.

Results

In total, 4615 images were analyzed from 100 APSP Web sites. Seven hundred eighty (16.9%) portrayed non-White skin tone, which was significantly less than expected based on US census data (23.7% non-White race) (P < 0.001). Online representation had the starkest disparity in hand surgery (8.65% non-White) and adult craniofacial (9.74% non-White). The only categories that showed no significant difference between representation and demographics included implant-based breast reconstruction (P = 0.32) and pediatric craniofacial (P = 0.93). Overall, the marketing materials demonstrated significantly lower representation of non-White skin compared with the census demographics by an absolute difference of −4.71% (P < 0.001).

Conclusions

Non-White patients are significantly underrepresented in advertising materials published by APSPs, indicating systemic racial biases. Patient-targeted advertising can be improved to promote equality in representation for patients seeking plastic and reconstructive surgery.
Outcomes of SARS-CoV-2 Infection in Unvaccinated Compared With Vaccinated Solid Organ Transplant Recipients: A Propensity Matched Cohort Study
Authors: Hall Victoria G. , Al-Alahmadi Ghadeer , Solera Javier T. , Marinelli Tina , Cardinal Heloise , Prasad G. V. Ramesh , De Serres Sacha A. , Isaac Debra , Mainra Rahul , Lamarche Caroline , Sapir-Pichhadze Ruth , Gilmour Susan , Matelski John , Humar Atul , Kumar Deepali
Published: May 2022

Background.

Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). Vaccination may mitigate this risk; however, immunogenicity appears to be significantly impaired, with reports of increased risk of breakthrough infection. It is unknown if vaccine breakthrough infections are milder or as severe as infections in unvaccinated patients.

Methods.

We performed a multicenter matched cohort study between March 2020 and September 2021 to assess influence of COVID-19 vaccination on outcomes of COVID-19 infection. Treatment characteristics and disease severity outcomes were compared on the basis of vaccine status; breakthrough infections versus unvaccinated infections. Variable ratio propensity score matching based on age, sex, transplant type, and number of comorbidities, was used to develop the analytic cohort. Logistic regression was used to assess the influence of vaccination status on the selected outcomes.

Results.

From a cohort of 511 SOT patients with COVID-19, we matched 77 partially or fully vaccinated patients with 220 unvaccinated patients. Treatment characteristics including use of dexamethasone, remdesivir, and antibiotics did not differ. Vaccinated participants were more likely to receive tocilizumab, 15 of 77 (19.5%) versus 5 of 220 (2.3%), P < 0.001. Disease severity outcomes including oxygen requirement, mechanical ventilation, and mortality were similar among medically attended vaccine breakthroughs compared with unvaccinated patients.

Conclusions.

SOT recipients who develop medically attended COVID-19 following 1- or 2-dose vaccination seem to have similar disease severity to unvaccinated patients who develop infection. This is consistent with the requirement that SOT recipients need 3 or more vaccine doses and emphasizes the importance of alternate strategies for this population.
Allergic reaction induced by subcutaneous administration of ketamine: a case report
Authors: Cordova Victor Hugo Schaly , Anzolin Ana Paula , Sant’Ana Marcia Kauer , Lacerda Acioly , Belmonte-de-Abreu Paulo Silva
Published: May 2022

Ketamine can be used for depression and suicidal ideation due to its effectiveness and low complication rates; moreover, allergic reactions are rare. Immediately after subcutaneous (SC) ketamine administration, a 22-year-old man rapidly developed hives on the trunk and face without oxygen desaturation. Symptoms disappeared after treatment with prednisolone. This case presents an allergic reaction to ketamine compatible with mast cell activation and release of preformed mediators, without being able to prove whether the event was mediated by immunoglobulin E. This is the only case reported to date of an allergic reaction to SC ketamine for psychiatric treatment.
Supercoiling-mediated feedback rapidly couples and tunes transcription
Authors: Johnstone Christopher P. , Galloway Kate E.
Published: May 2022

Transcription induces a wave of DNA supercoiling, altering the binding affinity of RNA polymerases and reshaping the biochemical landscape of gene regulation. As supercoiling rapidly diffuses, transcription dynamically reshapes the regulation of proximal genes, forming a complex feedback loop. The resulting intergene coupling may provide a mechanism to control transcriptional variance in engineered gene networks and explain the behavior of co-localized native circuits. However, a theoretical framework is needed for integrating both biophysical and biochemical transcriptional regulation to investigate the role of supercoiling-mediated feedback within multi-gene systems. Here, we model transcriptional regulation under the influence of supercoiling-mediated polymerase dynamics, allowing us to identify patterns of expression that result from physical intergene coupling and explore integration of this biophysical model with a set of canonical biochemical gene regulatory systems. We find that gene syntax—the relative ordering and orientation of genes—defines the expression profiles, variance, burst dynamics, and intergene correlation of two-gene systems. By applying our model to both a synthetic toggle switch and the endogenous zebrafish segmentation network, we find that supercoiling can enhance or weaken conventional biochemical regulatory strategies such as mRNA- and protein-mediated feedback loops. Together, our results suggest that supercoiling couples behavior between neighboring genes, representing a novel regulatory mechanism. Integrating biophysical regulation into the analysis and design of gene regulation provides a framework for enhanced understanding of native networks and engineering of synthetic gene circuits.
Distinct cytosolic complexes containing the type III secretion system ATPase resolved by 3D single-molecule tracking in liveYersinia enterocolitica
Authors: Prindle Joshua R , Wang Yibo , Rocha Julian , Diepold Andreas , Gahlmann Andreas
Published: May 2022

The membrane-embedded injectisome, the structural component of the virulence-associated type III secretion system (T3SS), is used by gram-negative bacterial pathogens to inject species-specific effector proteins into eukaryotic host cells. The cytosolic injectisome proteins are required for export of effectors and display both stationary, injectisome-bound populations as well as freely-diffusing cytosolic populations. How the cytosolic injectisome proteins interact with each other in the cytosol and associate with membrane-embedded injectisomes remains unclear. Here, we utilize 3D single-molecule tracking to resolve distinct cytosolic complexes of injectisome proteins in livingYersinia enterocoliticacells. Tracking of the eYFP-labeled ATPase,YeSctN, and its regulator,YeSctL, reveals that these proteins form a cytosolic complex with each other and then further withYeSctQ.YeSctNL andYeSctNLQ complexes can be observed both in wild type cells and in ΔsctDmutants, which cannot assemble injectisomes. In ΔsctQmutants, the relative abundance of theYeSctNL complex is considerably increased. These data indicate that distinct cytosolic complexes of injectisome proteins can form prior to injectisome binding, which has important implications for how injectisomes are functionally regulated.

Importance

Injectisomes are membrane-embedded, multiprotein assemblies used by bacterial pathogens to inject virulent effector proteins into eukaryotic host cells. Protein secretion is regulated by cytosolic proteins that dynamically bind and unbind at injectisomes. However, how these regulatory proteins interact with each other remains unknown. By measuring the diffusion rates of single molecules in living cells, we show that cytosolic injectisome proteins form distinct oligomeric complexes with each other prior to binding to injectisomes. We additionally identify the molecular compositions of these complexes and quantify their relative abundances. Quantifying to what extent cytosolic proteins exist as part of larger complexes in living cells has important implications for deciphering the complexity of biomolecular mechanisms. The results and methods reported here are thus relevant for advancing our understanding of how injectisomes, and related multiprotein assemblies, such as bacterial flagellar motors, are functionally regulated.
Promising efficacy of following a third dose of mRNA SARS-CoV-2 vaccination in patients treated with anti-CD20 antibody who failed 2-dose vaccination
Authors: Funakoshi Yohei , Yakushijin Kimikazu , Ohji Goh , Hojo Wataru , Sakai Hironori , Watanabe Marika , Kitao Akihito , Miyata Yoshiharu , Saito Yasuyuki , Kawamoto Shinichiro , Yamamoto Katsuya , Ito Mitsuhiro , Koyama Taiji , Imamura Yoshinori , Kiyota Naomi , Matsuoka Hiroshi , Mori Yasuko , Minami Hironobu
Published: May 2022

Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for S1 protein after third vaccination in 22 patients treated with anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving seroconversion rate in patients treated with anti-CD20 antibody who failed standard two-dose vaccination.
Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients
Authors: Thomson Tina , Prendecki Maria , Gleeson Sarah , Martin Paul , Spensley Katrina J , Cardoso De Aguiar Rute , Sandhu Bynvant , Seneschall Charlotte , Gan Jaslyn , Clarke Candice L. , Lewis Shanice , Pickard Graham , Thomas David , McAdoo Stephen P. , Lightstone Liz , Cox Alison , Kelleher Peter , Willicombe Michelle
Published: May 2022

Background

Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population.

Methods

724 kidney transplant recipients were prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their 1st dose of vaccine.

Results

586/724 (80.9%) patients were infection-naïve post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.

Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients who were seronegative post-V3. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. Anti-S post-V4 were sequentially greater in those seroconverting post V2- compared with V3-, and V3- compared with V4-, at 1561 (567-5211), 379 (101-851) and 19 (9.7-48) BAU/ml respectively.

T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type.

Conclusion

A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection.
PREVALENCE OF PRECONCEPTION CARE PROVISION IN KISUMU COUNTY-KENYA
Authors: Morema Everlyne N. , Senghor Morris , Ouma Collins
Published: May 2022

Background

‘Preconception care’ (PCC) is the provision of biomedical, behavioral and social health interventions to women and couples before conception occurs. The PCC, is valuable and key in preventing and controlling non-communicable diseases. There is the need for comprehensive preconception care provision in Kisumu County in order to promote healthy reproduction, improve maternal and neonatal health indicators in this and similar settings. Unfortunately, the current rate of provision for this service has not been documented in Kenya and more specifically in Kisumu County.

Methods

In a cross-sectional study, data on the provision of various services as per the recommended package for preconception care was collected in health facilities using a checklist. The targeted facilities (n=28) were selected using multistage sampling. The means for all of the services in the package was determined. The significance of the difference in the means was determined by one sample T-test at P-value ≤ 0.05

Results

Level of implementation of PCC was quite low at 39%. It was observed to be lower in the primary level facilities (KEPH level 2 and 3) at 34% and higher in referral facilities (level 4 and above) at 45%. The service with the highest implementation level was HIV prevention and management (84%) followed by sexually transmitted diseases (80%) and vaccination services (75%). The service with lowest level of implementation was environmental risk exposure reduction at 13% for level 2 and 3 followed by management of mental health disorders.

Conclusion

Provision of PCC was relatively low at 39% and provision was fragmented. Provision differed across service levels and care packages.
Stomatal regulators are co-opted for seta development in the astomatous liverwortMarchantia polymorpha
Authors: Moriya Kenta C. , Shirakawa Makoto , Loue-Manifel Jeanne , Matsuda Yoriko , Lu Yen-Ting , Tamura Kentaro , Oka Yoshito , Matsushita Tomonao , Hara-Nishimura Ikuko , Ingram Gwyneth , Nishihama Ryuichi , Goodrich Justin , Kohchi Takayuki , Shimada Tomoo
Published: May 2022

The evolution of special types of cells requires the acquisition of new gene regulatory networks controlled by transcription factors (TFs). In stomatous plants, a TF module formed by subfamilies Ia and IIIb basic helix-loop-helix TFs (Ia-IIIb bHLH) regulates stomatal formation; however, how this module evolved during land plant diversification remains unclear. Here, we show that, in the astomatous liverwortMarchantia polymorpha, a Ia-IIIb bHLH module regulates the development of a unique sporophyte tissue, the seta, which is found in mosses and liverworts. The sole Ia bHLH gene, MpSETA, and a IIIb bHLH gene, MpICE2, regulate the cell division and/or differentiation of seta lineage cells. MpSETA can partially replace the stomatal function of Ia bHLH TFs inArabidopsis thaliana, suggesting that a common regulatory mechanism underlies the setal and stomatal formation. Our findings reveal the co-option of a Ia-IIIb bHLH TF module for regulating cell fate determination and/or cell division of distinct types of cells during land plant evolution.
Isotope-based visualization of element distribution in phloem provides functional evidence for the operation of SOS1 Na+/H+ exchangers in mature zones of Arabidopsis root
Authors: Sugita Ryohei , Ogura Takaaki , Kobayashi Natsuko I. , Gill Muhammad B. , Shabala Lana , Nakanishi Tomoko M. , Shabala Sergey , Tanoi Keitaro
Published: May 2022

In the phloem, various solutes such as photosynthates, mineral nutrients, or toxic elements move from the source organs to sinks. One of them is the root. While this process may mediate significant quantities of solutes delivered to the root, it is unclear how the solutes are distributed along the root axis. To elucidate the distributing pattern of solutes, we visually analyzed the movement of solutes in Arabidopsis roots using a radioisotope imaging technique. The distribution patterns fell into four different groups: (1) root tip accumulation for 14C-photosynthates, 28Mg2+, 32PO43-, and 35SO42-; (2) homogenous distribution along the root axis for 42K+ and 137Cs+; (3) no detectable accumulation in the root for 45Ca2+ and 59Fe2+; and (4) transient accumulation in the root for 22Na+. The latter phenomenon was explored in more detail using Arabidopsis knockout mutants lacking functional sodium efflux transporter SOS1 (operating as Na+/H+ exchanger). By utilizing a non-invasive microelectrode MIFE ion flux measuring technique, we found that Na+ efflux was active in the mature root zone of wild-type Arabidopsis plants but not in root apex as initially thought, and that in sos1 mutants lacking functional Na+/H+ exchangers, shoot-derived 22Na+ remained in the root. These findings challenge the notion that Na+ exclusion via SOS1 is confined to the root apex and demonstrates the power of combining the radioisotope imaging technique and the MIFE ion flux measuring technique to study the kinetics of ion transport in the root and root-to-shoot communication.
Preserved executive control in ageing: The role of literacy experience
Authors: Pérez Ana I. , Fotiadou Georgia , Tsimpli Ianthi
Published: May 2022

Healthy ageing is commonly accompanied by cognitive decline affecting several domains such as executive control, whereas certain verbal skills remain relatively preserved. Interestingly, recent scientific research has shown that some intellectual activities may be linked to beneficial effects, delaying or even alleviating cognitive decline in the elderly. Thirty young (age: M = 23) and thirty old (age: M = 66) adults were assessed in executive control (switching) and literacy experience (print exposure). First, we tried to confirm whether healthy ageing was generally associated with deficits in switching by looking at mixing cost effects, to then investigate if individual differences in print exposure explained variation in that age-related mixing costs. Both accuracy and reaction times mixing cost indexes demonstrated larger cost in old (but not in young) adults when switching from local to global information. More importantly, this cost effect disappeared in old adults with higher print exposure (reaction times). Our findings suggest literacy experience accumulated across the life-span may act as a cognitive reserve proxy to prevent executive control decline.
In-situ energy budget of needle-leaves reveals shift from evaporative to ‘air cooling’ under drought
Authors: Muller Jonathan D. , Rotenberg Eyal , Tatarinov Fyodor , Oz Itay , Yakir Dan
Published: May 2022

The modulation of the leaf energy budget and the balance between its sensible heat (H) and latent heat (LE) fluxes is vital for vegetation functioning and survival, as it is linked to maintaining leaf temperature below the thermal threshold, an increasingly important mechanism under a drying and warming climate, when evaporative cooling is suppressed.

Combining measurements and theoretical estimates using a new methodology, we obtained rare and comprehensive energy budgets of leaves on twigs under field conditions in droughted and non-droughted plots of a semi-arid pine forest with low and high evapotranspiration rates, respectively.

An examination of all components of the needle-leaf energy budget indicated that under the same radiative load, leaf cooling shifts from nearly equal contributions to H and LE in non-droughted trees to almost exclusively H in droughted ones while maintaining a similar leaf temperature.

This LE-to-H shift in leaves of droughted trees highlights the efficiency of the ‘air cooling’ mechanism in maintaining temperature, which can enhance the resilience of trees to drying conditions. Additionally, leaf energy budgets are a fundamental tool to help understand leaf cooling and aerodynamic resistance under field conditions, and to improve modelling of ecosystem activity and its effect on the climate system.
Differential activation of NLRP3 inflammasome by Acinetobacter baumannii strains
Authors: Li Fei-Ju , Starrs Lora , Mathur Anukriti , Ishii Hikari , Man Si Ming , Burgio Gaetan
Published: May 2022

Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen with growing clinical significance globally. A. baumannii has an exceptional ability to rapidly develop drug resistance. It is frequently responsible for ventilator-associated pneumonia in clinical settings and inflammation resulting in severe sepsis. The inflammatory response is mediated by host pattern-recognition receptors and the inflammasomes. Inflammasome activation triggers inflammatory responses, including the secretion of the pro-inflammatory cytokines IL-1β and IL-18, the recruitment of innate immune effectors against A. baumannii infection, and the induction programmed cell death by pyroptosis. An important knowledge gap is how variation among clinical isolates affects the host’s innate response and activation of the inflammasome during A. baumannii infection. In this study, we compared nine A. baumannii strains, including clinical locally-acquired isolates, in their ability to induce activation of the inflammasome and programmed cell death pathway in primary macrophages and mice. We found a striking variability in survival outcomes of mice and bacterial dissemination in organs among three ATCC A. baumannii strains, likely due to the differences in virulence between strains. Interestingly, we found a stark contrast in activation of the NLRP3 inflammasome pathway, the non-canonical caspase-11 pathway, plasmatic secretion of the pro-inflammatory cytokines IL-1β and IL-18 between A. baumannii strains. Our study highlights the importance of utilising multiple bacterial strains and clinical isolates with differential virulence to investigate the innate immune response to A. baumannii infection.
Genetic architectures of floral pigment and patterning in hybrid monkeyflowers
Authors: Cooley Arielle M. , Schlutius Caroline , Matthews Melia , Zheng Xingyu , Thomas Daniel , Edger Patrick P. , Platts Adrian E. , LaFountain Amy , George Logan , Williams Aaron , Hundley Douglas , Yuan Yao-Wu , Twyford Alex , Puzey Joshua R.
Published: May 2022

Hybridization generates inter-genomic interactions, which may result in unique traits not seen in either parent species. Here we explore the genetic basis of both carotenoid and anthocyanin floral pigmentation in hybrids between monkeyflower speciesMimulus cupreusandM. luteusvar.variegatus. Mimulus cupreushas abundant yellow carotenoid pigmentation in its petal lobes, whileM. l. variegatushas a derived reduction in carotenoid intensity. Thus, as expected, carotenoid intensity segregates in an F2 hybrid population. More surprisingly, both species appear to have petal lobes solidly and identically covered in magenta anthocyanin pigment (which, when overlaid on the bright yellow carotenoid background, leads to an orange color inM. cupreus), yet F1 and F2 hybrids exhibit novel and complex spatial patterns of anthocyanin spotting. A rare yellow morph ofM. cupreus, which lacks petal anthocyanins, also generates spatially patterned offspring when hybridized withM. l. variegatus. We use this cross, together with newly developed high-quality genome assembly ofM. l. luteusand image analysis tools, to investigate the genetic architecture of color and pattern variation in an F2 hybrid population. We report a single QTL, containing theBeta-carotene hydroxylase(BCH) gene, associated with the non-patterned carotenoid reduction inM. l. variegatus. HPLC shows that relative beta-carotene abundance differs between dark yellow and light yellow petals, supporting a causal role forBCH. The presence versus absence of petal lobe anthocyanin segregates in a 3:1 ratio, and we report (as expected) an associated QTL encompassing the anthocyanin activatorMYB5a/NEGANwhich has previously been shown to be both necessary and sufficient to activate petal lobe anthocyanins inM. l. variegatus. Anthocyanin patterning was more complex, with seven QTLs associated with five quantitative patterning traits on the upper petals; 11 on the lower petals; and three qualitative whole-flower patterning traits. Although power was too limited to effectively test for epistatic interactions in this cross, the QTLs provide candidate genomic regions for further investigating the molecular mechanisms of spatially complex floral color patterning, and multiple candidate genes are identified including anthocyanin activators and an anthocyanin repressor.
The effect of external lateral stabilization on ankle moment control during steady-state walking
Authors: van Leeuwen A.M. , van Dieën J.H. , Bruijn S.M.
Published: May 2022

External lateral stabilization can help identify stability control mechanisms during steady-state walking. The degree of step-by-step foot placement control and step width are known to decrease when walking with external lateral stabilization. Here, we investigated the effect of external lateral stabilization on ankle moment control in healthy participants. Ankle moment control complements foot placement, by allowing a corrective center-of-pressure shift once the foot has been placed. This is reflected by a model predicting this center-of-pressure shift based on the preceding foot placement error. Here, the absolute explained variance accounted for by this model decreased when walking with external lateral stabilization. In other words, we found a reduction in the contribution of step-by-step ankle moment control to mediolateral gait stability when externally stabilized. Concurrently, foot placement error and the average center-of-pressure shift remained unchanged.
Long-term population decline of a genetically homogenous continental-wide top Arctic predator
Authors: Gousy-Leblanc Marianne , Therrien Jean-François , Broquet Thomas , Rioux Delphine , Curt-Grand-Gaudin Nadine , Tissot Nathalie , Tissot Sophie , Szabo Ildiko , Wilson Laurie , Evans Jack T. , Bowes Victoria , Gauthier Gilles , Wiebe Karen L. , Yannic Glenn , Lecomte Nicolas
Published: May 2022

Genetic analysis can provide valuable information for conservation programs by unraveling the demographic trajectory of populations, by estimating effective population size, or by inferring genetic differentiation between populations. Here, we investigated the genetic differentiation within the Snowy Owl (Bubo scandiacus), a species identified as vulnerable by the IUCN, to (i) quantify connectivity among wintering areas, (ii) to evaluate current genetic diversity and effective population size and (iii) to infer changes in the historical effective population size changes from the last millennia to the recent past. The Snowy Owl, a highly mobile top predator, breeds across the Arctic tundra which is a region especially sensitive to current climate change. Using SNP-based analyses on Snowy Owls sampled across the North American nonbreeding range, we found an absence of genetic differentiation among individuals located up to 4,650 km apart. Our results suggest high genetic intermixing and effective dispersal at the continental scale despite documented philopatry to nonbreeding sites in winter. Reconstructing the population demographic indicated that North American Snowy Owls have been steadily declining since the Last Glacial Maximum ca 20,000 years ago and concurrently with global increases in temperature. Conservation programs should now consider North American Snowy Owls as a single, genetically homogenous continental-wide population which is most likely sensitive to the long-term global warming occurring since the Last Glacial Maximum.
Discordant effects of resource limitation on host survival and systemic pathogen growth in Drosophila-bacteria infection models: resistance vs. tolerance
Authors: Basu Aabeer , Singh Aparajita , Sehgal Suhaas , Madaan Tanvi , Prasad Nagaraj Guru
Published: May 2022

In the experiments presented here, we explore the effect of resource limitation, in form of starvation (which leads to decrease in accessible resources and depletion of reserves) and sexual activity (which leads to reallocation of resources from somatic defence towards reproduction), on immune function of female Drosophila melanogaster flies. We infected females with five bacterial pathogens and measured their post-infection survival when subjected to either starvation or sexual activity (mating). Additionally, we measured within host pathogen levels in case of three of these pathogens. Based on previous literature, we predicted that both modes of resource limitation will increase post-infection mortality, but only sexual activity will lead to increase of pathogen load (because of compromised immune function), while starvation will either not affect or reduce pathogen loads (because of reduced availability of resources for the pathogen to proliferate within the host). Our results indicate that both starvation and sexual activity can lead to increased within-host pathogen levels, in addition to increased post-infection mortality, but in a pathogen-specific manner.
ChemPert: mapping between chemical perturbation and transcriptional response for non-cancer cells
Authors: Zheng Menglin , Okawa Satoshi , Bravo Miren , Chen Fei , Martínez-Chantar María-Luz , del Sol Antonio
Published: May 2022

Prior knowledge of perturbation data can significantly assist in inferring the relationship between chemical perturbations and their specific transcriptional response. However, current databases mostly contain cancer cell lines, which are unsuitable for the aforementioned inference in non-cancer cells. Here we present ChemPert (https://chempert.uni.lu/), a database consisting of 82270 transcriptional signatures across 167 non-cancer cell types, enabling more accurate predictions of perturbation responses and drugs compared to cancer databases in non-cancer cells. In particular, ChemPert correctly predicted drug effects for treating non-alcoholic steatohepatitis and novel drugs for osteoarthritis. Overall, ChemPert provides a valuable resource for drug discovery in non-cancer diseases.
Correcting gradient-based interpretations of deep neural networks for genomics
Authors: Majdandzic Antonio , Rajesh Chandana , Koo Peter K.
Published: May 2022

Post-hoc attribution methods are widely applied to provide insights into patterns learned by deep neural networks (DNNs). Despite their success in regulatory genomics, DNNs can learn arbitrary functions outside the probabilistic simplex that defines one-hot encoded DNA. This introduces a random gradient component that manifests as noise in attribution scores. Here we demonstrate the pervasiveness of off-simplex gradient noise for genomic DNNs and introduce a statistical correction that is effective at improving the interpretability of attribution methods.