bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational analysis of sense-antisense chimeric transcripts reveals their potential regulatory features and the landscape of expression in human cells
Authors: Mukherjee Sumit , Detroja Rajesh , Balamurali Deepak , Matveishina Elena , Medvedeva Yulia A , Valencia Alfonso , Gorohovski Alessandro , Frenkel-Morgenstern Milana
Published: August 2021

Many human genes are transcribed from both strands and produce sense-antisense gene pairs. Sense-antisense (SAS) chimeric transcripts are produced upon the coalescing of exons/introns from both sense and antisense transcripts of the same gene. SAS chimera was first reported in prostate cancer cells. Subsequently, numerous SAS chimeras have been reported in the ChiTaRS-2.1 database. However, the landscape of their expression in human cells and functional aspects are still unknown. We found that longer palindromic sequences are a unique feature of SAS chimeras. Structural analysis indicates that a long hairpin-like structure formed by many consecutive Watson-Crick base pairs appears because of these long palindromic sequences, which possibly play a similar role as double-stranded RNA (dsRNA), interfering with gene expression. RNA–RNA interaction analysis suggested that SAS chimeras could significantly interact with their parental mRNAs, indicating their potential regulatory features. Here, 267 SAS chimeras were mapped in RNA-seq data from 16 healthy human tissues, revealing their expression in normal cells. Evolutionary analysis suggested the positive selection favoring sense-antisense fusions that significantly impacted the evolution of their function and structure. Overall, our study provides detailed insight into the expression landscape of SAS chimeras in human cells and identifies potential regulatory features.
The F-box E3 ubiquitin ligase BAF1 mediates the degradation of the brassinosteroid-activated transcription factor BES1 through selective autophagy in Arabidopsis
Authors: Wang Ping , Nolan Trevor M , Clark Natalie M , Jiang Hao , Montes-Serey Christian , Guo Hongqing , Bassham Diane C , Walley Justin W , Yin Yanhai
Published: August 2021

Brassinosteroids (BRs) regulate plant growth, development, and stress responses by activating the core transcription factor BRI1-EMS-SUPPRESSOR1 (BES1), whose degradation occurs through the proteasome and autophagy pathways. The E3 ubiquitin ligase(s) that modify BES1 for autophagy-mediated degradation remain to be fully defined. Here, we identified an F-box family E3 ubiquitin ligase named BES1-ASSOCIATED F-BOX1 (BAF1) in Arabidopsis thaliana. BAF1 interacts with BES1 and mediates its ubiquitination and degradation. Our genetic data demonstrated that BAF1 inhibits BR signaling in a BES1-dependent manner. Moreover, BAF1 targets BES1 for autophagic degradation in a selective manner. BAF1-triggered selective autophagy of BES1 depends on the ubiquitin binding receptor DOMINANT SUPPRESSOR OF KAR2 (DSK2). Sucrose starvation-induced selective autophagy of BES1, but not bulk autophagy, was significantly compromised in baf1 mutant and BAF1-ΔF (BAF1 F-box decoy) overexpression plants, but clearly increased by BAF1 overexpression. The baf1 and BAF1-ΔF overexpression plants had increased BR-regulated growth but were sensitive to long-term sucrose starvation, while BAF1 overexpression plants had decreased BR-regulated growth but were highly tolerant of sucrose starvation. Our results not only established BAF1 as an E3 ubiquitin ligase that targets BES1 for degradation through selective autophagy pathway, but also revealed a mechanism for plants to reduce growth during sucrose starvation.
Immunocapture of dsRNA-bound proteins provides insight into Tobacco rattle virus replication complexes and reveals Arabidopsis DRB2 to be a wide-spectrum antiviral effector
Authors: Incarbone Marco , Clavel Marion , Monsion Baptiste , Kuhn Lauriane , Scheer Hélène , Vantard Émilie , Poignavent Vianney , Dunoyer Patrice , Genschik Pascal , Ritzenthaler Christophe
Published: August 2021

Plant RNA viruses form organized membrane-bound replication complexes to replicate their genomes. This process requires virus- and host-encoded proteins and leads to the production of double-stranded RNA (dsRNA) replication intermediates. Here, we describe the use of Arabidopsis thaliana expressing GFP-tagged dsRNA-binding protein (B2:GFP) to pull down dsRNA and associated proteins in planta upon infection with Tobacco rattle virus (TRV). Mass spectrometry analysis of the dsRNA-B2:GFP-bound proteins from infected plants revealed the presence of viral proteins and numerous host proteins. Among a selection of nine host candidate proteins, eight showed relocalization upon infection, and seven of these colocalized with B2-labeled TRV replication complexes. Infection of A. thaliana T-DNA mutant lines for eight such factors revealed that genetic knockout of dsRNA-BINDING PROTEIN 2 (DRB2) leads to increased TRV accumulation and DRB2 overexpression caused a decrease in the accumulation of four different plant RNA viruses, indicating that DRB2 has a potent and wide-ranging antiviral activity. We propose B2:GFP-mediated pull down of dsRNA to be a versatile method to explore virus replication complex proteomes and to discover key host virus replication factors. Given the universality of dsRNA, development of this tool holds great potential to investigate RNA viruses in other host organisms.
Leaf herbivory counteracts nematode-triggered repression of jasmonate-related defenses in tomato roots
Authors: Martínez-Medina Ainhoa , Mbaluto Crispus M , Maedicke Anne , Weinhold Alexander , Vergara Fredd , van Dam Nicole M
Published: August 2021

Shoot herbivores may influence the communities of herbivores associated with the roots via inducible defenses. However, the molecular mechanisms and hormonal signaling underpinning the systemic impact of leaf herbivory on root-induced responses against nematodes remain poorly understood. By using tomato (Solanum lycopersicum) as a model plant, we explored the impact of leaf herbivory by Manduca sexta on the performance of the root knot nematode Meloidogyne incognita. By performing glasshouse bioassays, we found that leaf herbivory reduced M. incognita performance in the roots. By analyzing the root expression profile of a set of oxylipin-related marker genes and jasmonate root content, we show that leaf herbivory systemically activates the 13-Lipoxigenase (LOX) and 9-LOX branches of the oxylipin pathway in roots and counteracts the M. incognita-triggered repression of the 13-LOX branch. By using untargeted metabolomics, we also found that leaf herbivory counteracts the M. incognita-mediated repression of putative root chemical defenses. To explore the signaling involved in this shoot-to-root interaction, we performed glasshouse bioassays with grafted plants compromised in jasmonate synthesis or perception, specifically in their shoots. We demonstrated the importance of an intact shoot jasmonate perception, whereas having an intact jasmonate biosynthesis pathway was not essential for this shoot-to-root interaction. Our results highlight the impact of leaf herbivory on the ability of M. incognita to manipulate root defenses and point to an important role for the jasmonate signaling pathway in shoot-to-root signaling.
Cytological Observation of the Infectious Process of Venturia carpophila on Peach Leaves
Authors: Zhou Yang , Zhang Lei , Ji Chuan-Ya , Chaisiri Chingchai , Yin Liang-Fen , Yin Wei-Xiao , Luo Chao-Xi
Published: August 2021

Peach scab caused by Venturia carpophila is one of the most destructive fungal diseases of peach worldwide, and it seriously affects peach production. Until now,the infectious process and pathogenesis of V. carpophila on peach have remained unclear. Here we present the infection behavior of V. carpophila at the ultrastructural and cytological levels in peach leaves with combined microscopic investigations (i.e., light microscopy, confocal laser scanning microscopy, scanning electron microscopy, and transmission electron microscopy). V. carpophila germinated at the tip of conidia and produced short germ tubes on peach leaf surfaces at 2 days post inoculation (dpi). At 3 dpi, swollen tips of germ tubes differentiated into appressoria. At 5 dpi, penetration pegs produced by appressoria broke through the cuticle layer and then differentiated into thick subcuticular hyphae in the pectin layer of the epidermal cell walls. At 10 dpi, the subcuticular hyphae extensively colonized in the pectin layer. The primary hyphae ramified into secondary hyphae and proliferated along with the incubation. At 15 dpi, the subcuticular hyphae divided laterally to form stromata between the cuticle layer and the cellulose layer of the epidermal cells. At 30 dpi, conidiophores developed from the subcuticular stromata. Finally, abundant conidiophores and new conidia appeared on leaf surfaces at 40 dpi. These results provide useful information for further a understanding of V. carpophila pathogenesis.
The Sequence and Integrated Analysis of Competing Endogenous RNAs Originating from Tea Leaves Infected by the Pathogen of Tea Leaf Spot, Didymella segeticola
Authors: Wang Yu , Yang Yuanyou , Jiang Xinyue , Shi Jiayan , Yang Yuqin , Jiang Shilong , Li Zhong , Wang Delu , Chen Zhuo
Published: August 2021

Tea leaf spot, caused by Didymella segeticola, is an important disease which negatively affects the productivity and the quality of tea leaves. During infection by the pathogen, competing endogenous RNAs (ceRNAs) from tea leaves could contribute to achieving pathogenicity. In this study, circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs), constituting ceRNAs, which share binding sites on microRNAs (miRNAs), and messenger RNAs (mRNAs) from infected and uninfected leaves of tea (Camellia sinensis ‘Fuding-dabaicha’) were sequenced and analyzed, and the identity and expression levels of the target genes of miRNA–mRNA and miRNA–lncRNA/circRNA were predicted. Analysis indicated that 10 mRNAs were bound by 20 miRNAs, 66 lncRNAs were bound by 40 miRNAs, and 17 circRNAs were bound by 29 miRNAs, respectively. For the regulation modes of ceRNAs, five ceRNA pairs were identified by the correlation analysis of lncRNA–miRNA–mRNA. For instance, expression of the xyloglucan endotransglycosylase gene in infected leaves was downregulated at the level of mRNA through miRNA PC-5p-3511474_3 binding with lncRNA TEA024202.1:MSTRG.37074.1. Gene annotation indicated that expression of this gene was significantly enriched in cell wall biogenesis and in the pathway of plant hormone signal transduction. The functional analysis of ceRNAs isolated from infected tea leaves will provide a valuable resource for future research on D. segeticola pathogenicity.
Qing‐Fei‐Pai‐Du decoction and wogonoside exert anti‐inflammatory action through down‐regulating USP14 to promote the degradation of activating transcription factor 2
Authors: Xu Xin , Xia Jun , Zhao Shiyi , Wang Qun , Ge Guangbo , Xu Feng , Liu Xia , Zhang Weidong , Yang Yili
Published: August 2021

COVID‐19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing‐Fei‐Pai‐Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune‐related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium‐induced intestinal inflammation in mice. It inhibited the production of pro‐inflammatory cytokines IL‐6 and TNFα, and promoted the expression of anti‐inflammatory cytokine IL‐10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS‐stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half‐life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down‐regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal‐specific KLHL5 deficiency, a CUL3‐interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3‐KLHL5 may function as an E3 for ATF2 degradation.
Rising Trends in the Incidence of Shoulder Dystocia and Development of a Novel Shoulder Dystocia Risk Score Tool: A Nationwide Population-Based Study of 800,484 Finnish Deliveries
Authors: Heinonen Karin , Saisto Terhi , Gissler Mika , Kaijomaa Marja , Sarvilinna Nanna
Published: August 2021

(Abstracted from Acta Obstet Gynecol Scand 2021;100:538–547)

Shoulder dystocia is an unpredictable, obstetric emergency. Its incidence has been reported to range from 0.1% up to 3.0%.
Exome Sequencing Analysis on Products of Conception: A Cohort Study to Evaluate Clinical Utility and Genetic Etiology for Pregnancy Loss
Authors: Zhao Chen , Chai Hongyan , Zhou Qinghua , Wen Jiadi , Reddy Uma M. , Kastury Rama , Jiang Yonghui , Mak Winifred , Bale Allen E. , Zhang Hui , Li Peining
Published: August 2021

(Abstracted from Genet Med 2021;2:435–442)

Genetic variants are known to cause pregnancy loss. New data from exome sequencing studies have reported that exome sequencing may be a useful tool in identifying causes of pregnancy loss.
Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma
Authors: Farinazzo Eleonora , Zelin Enrico , Agozzino Marina , Papa Giovanni , Pizzichetta Maria Antonietta , di Meo Nicola , Zalaudek Iris
Published: August 2021

We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already after the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nevi and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice.
Primary Cutaneous Gamma-Delta T-Cell Lymphoma Mimicking anaplastic lymphoma kinase-1-Negative Anaplastic Large Cell Lymphoma: A Case Report
Authors: Meawad Hany , Song Joo Y. , Ulrickson Matthew L. , Weisenburger Dennis D.
Published: August 2021

Primary cutaneous gamma-delta T-cell lymphoma is a rare and aggressive neoplasm, representing less than 1% of all cutaneous T-cell lymphomas. In this article, we report the case of a 49-year-old woman who presented with a history of generalized skin rash and a recent mass on the left upper extremity, as well as right inguinal soft tissue swelling and splenomegaly. Histologic examination of the mass revealed a diffuse subcutaneous infiltrate of large anaplastic and CD30-positive lymphoid cells with rimming of the adipocytes. This case demonstrates unusual cytologic features in primary cutaneous gamma-delta T-cell lymphoma that mimic the features of anaplastic lymphoma kinase-1-negative anaplastic large-cell lymphoma.
Localized Medium-Vessel Vasculitis From a Tick Bite
Authors: Rice Shauna , Clark Mary , Robinson-Bostom Leslie
Published: August 2021

Tick bites are known to induce a variety of inflammatory reaction patterns. Here, we present a novel case of medium-vessel vasculitis as a localized response to a known tick bite. It is important to recognize the histology associated with a tick bite response to prevent misdiagnosis and potential overtreatment of a vasculitic condition.
Chronic thromboembolic pulmonary hypertension anno 2021
Authors: Nossent Esther J. , Meijboom Lilian J. , Bogaard Harm J. , Klok Frederikus A.
Published: August 2021

Purpose of review

In the past decades, the diagnostic and therapeutic management of chronic thromboembolic pulmonary hypertension (CTEPH) has been revolutionized.

Recent findings

Advances in epidemiological knowledge and follow-up studies of pulmonary embolism patients have provided more insight in the incidence and prevalence. Improved diagnostic imaging techniques allow accurate assessment of the location and extend of the thromboembolic burden in the pulmonary artery tree, which is important for the determination of the optimal treatment strategy. Next to the pulmonary endarterectomy, the newly introduced technique percutaneous pulmonary balloon angioplasty and/or P(A)H-targeted medical therapy has been shown to be beneficial in selected patients with CTEPH and might also be of importance in patients with chronic thromboembolic pulmonary vascular disease.

In this era of a comprehensive approach to CTEPH with different treatment modalities, a multidisciplinary approach guides management decisions leading to optimal treatment and follow-up of patients with CTEPH.
RELATIONSHIP BETWEEN MYOPIC CHOROIDAL NEOVASCULARIZATION ACTIVITY AND PERFORATING SCLERAL VESSELS IN HIGH MYOPIA
Authors: Ruiz-Medrano Jorge , Almazan-Alonso Elena , Flores-Moreno Ignacio , Puertas Mariluz , García-Zamora María , Ruiz-Moreno José M.
Published: August 2021

Purpose:

To study perforating scleral vessels (PSVs) in patients with high myopia using swept-source optical coherence tomography and to determine their relationship with myopic choroidal neovascularization (mCNV) and its activity.

Methods:

Retrospective analysis of patients with high myopia (≥−6 D or ≥26 mm of axial length) using multimodal imaging. The presence of PSVs and mCNV was assessed using swept-source optical coherence tomography images (TRITON; Topcon Corporation, Japan).

Results:

Five hundred sixty-four eyes from 297 highly myopic patients were studied. One hundred fifty-five eyes (27.5%) showed signs of mCNV while PSVs were found in 500 eyes (88.6%). Perforating scleral vessels were found in 93.5% (145/155) of eyes with mCNV, and they were under or in contact with the mCNV in 80.6% (117/145). The mean number of intravitreal injections received by patients with mCNV was 4.06 ± 4.17 along 66.9 ± 4.1 months of follow-up. The number of injections per year was 1.32 ± 1.56, the mean number of relapses was 1.11 ± 1.83, and the mean number of relapses per year was 0.25 ± 0.41.

Conclusion:

Perforating scleral vessels are more common among highly myopic patients suffering from neovascular complications. Myopic CNV complexes that are coincident with PSVs on optical coherence tomography show higher rates of activity, needing more injections to control them and being more prone to relapses.
Second-generation capsular anchor for subluxated lenses: first clinical results
Authors: Belkin Avner , Yehezkeli Veronika , Assia Ehud I.
Published: August 2021

Purpose:

To evaluate the use of the second-generation capsular anchor in the treatment of subluxated crystalline and synthetic intraocular lenses.

Setting:

Department of Ophthalmology, Meir Medical Center, Kfar Saba, Israel.

Design:

Prospective interventional study.

Methods:

This study evaluated the second-generation capsular anchor, a 3D poly(methyl methacrylate) intraocular implant designed to anchor the lens capsule to the sclera. All surgeries were performed by a single surgeon. Intraoperative and postoperative complications were recorded. Corrected distance visual acuity, lens centration, and lens tilt were assessed at the final follow-up of 3 months.

Results:

10 eyes of 10 patients were included in this study. Mean age was 56.2 (22 to 87) years. The reasons for the lack of zonular support were pseudoexfoliation in 3 cases, trauma in 3 cases, and Marfan, ectopia lentis, and pathologic myopia (1 case each). In 1 case, pseudoexfoliation and a history of recent trauma coexisted. 8 of the 10 surgeries were due to subluxation of crystalline lenses and 2 due to subluxation of intraocular lenses. Vision improved in all patients after surgery. Centration of the IOLs was excellent in all patients at the third postoperative month. One patient developed a retinal detachment at the third postoperative week and underwent successful surgery, and 1 patient developed macular edema at the fifth postoperative month, which resolved with topical medication.

Conclusions:

The second-generation capsular anchor, designed to provide significant improvements over the first-generation device, is effective in fixating the capsular bag to the scleral wall in cases with inadequate capsular support.
Predictive accuracy of an intraoperative aberrometry device for a new monofocal intraocular lens
Authors: Spekreijse Lindsay S. , Bauer Noel J.C. , van den Biggelaar Frank J.H.M. , Simons Rob W.P. , Veldhuizen Claudette A. , Berendschot Tos T.J.M. , Nuijts Rudy M.M.A.
Published: August 2021

Purpose:

To evaluate refractive outcomes for the Clareon monofocal intraocular lens (IOL) in terms of achieved target refraction for the ORA (ALCON) intraoperative wavefront aberrometry device and preoperative noncontact biometry.

Setting:

University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands.

Design:

Prospective observational clinical trial.

Methods:

Patients with bilateral age-related cataracts undergoing phacoemulsification, either by delayed sequential surgery or on the same day, were included in the study. Exclusion criteria were an increased risk for refractive surprise or complicated surgery. Implanted IOL power was based on noncontact optical biometry data using the Barrett Universal II (BU-II) formula, optimized for the Clareon IOL. Postoperative subjective refraction was measured 4 to 6 weeks after surgery. Catquest-9SF questionnaires were completed preoperatively and 3 months after surgery.

Results:

100 eyes (51 patients) were included. The percentages of eyes within 1.0 diopters (D), 0.75 D, 0.50 D, and 0.25 D of target for ORA vs BU-II were 84% (84 eyes), 72% (72 eyes), 57% (57 eyes), and 21% (21 eyes) vs 97% (97 eyes), 88% (88 eyes), 77% (77 eyes), and 53% (53 eyes), respectively. Mean absolute prediction error was significantly higher for ORA vs preoperative biometry (P < .001). After global optimization, the prediction accuracy of ORA improved significantly (P < .001). Catquest-9SF questionnaires showed improved levels of ability at 3 months after surgery (P < .001).

Conclusions:

This study showed lower percentages of eyes within target refraction for ORA (prior to lens constant optimization) compared with the BU-II formula when implanting the Clareon IOL. However, prediction accuracy of ORA improved significantly after global optimization. Therefore, further intraoperative measurements, postoperative measurements, and optimization are needed to improve the ORA prediction for this IOL.
A Review of the Clinician’s Role in Women’s Weight Management and Implications for Women’s Health and Pregnancy Outcomes
Authors: Nelson Rachel S. , Schulkin Jay , Power Michael L.
Published: August 2021

Importance

Ten years have passed since the Institute of Medicine (IOM) released its recommendations for gestational weight gain (GWG), based on a woman's prepregnancy body mass index. Despite this, the majority of women do not gain the appropriate gestational weight; most women gain too much weight, and a small but substantial number gain too little.

Objectives

We review the literature concerning GWG, the opinions and practices of clinicians in managing their patients' weight, and how these practices are perceived by patients. We also review several randomized control trials that investigate the efficacy of clinical intervention in managing GWG.

Evidence Acquisition

A literature review search was conducted with no limitations on the number of years searched.

Results

The number of clinicians who are aware of and use the IOM recommendations has increased, but the prevalence of inappropriate GWG has not decreased. Clinicians report feeling less than confident in their ability to have an impact on their patients' weight gain, and there are discrepancies between what clinicians and patients report regarding counseling. Many randomized control trials demonstrate a beneficial impact of clinical intervention, highlighting the importance of collaboration and technology to provide educational information and support throughout a pregnancy.

Conclusions

Pregnancy provides an opportunity for clinicians to have open and direct conversations with their patients about their weight. Providing clinicians with the tools, skillset, and confidence to assist in the management of GWG is essential to the health of women and their children, and warrants further investigation.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this review, clinicians should be better able to identify risk factors of inappropriate GWG and associated complications; summarize current literature on how both clinicians and patients perceive GWG; explain how to assess appropriate GWG on an individual basis based on IOM recommendations; and describe methods to help women achieve appropriate GWG.
Depletion of Aneuploid Cells in Human Embryos and Gastruloids
Authors: Yang Min , Rito Tiago , Metzger Jakob , Naftaly Jeffrey , Soman Rohan , Hu Jianjun , Albertini David F. , Barad David H. , Brivanlou Ali H. , Gleicher Norbert
Published: August 2021

(Abstracted from Nat Cell Biol 2021;23:314–321)

Despite it being current practice in vitro fertilization (IVF) protocols to exclude aneuploid embryos diagnosed through preimplantation genetic testing (PGT-A), it remains controversial whether or not this improves IVF outcomes. Both IVF pregnancies and spontaneous pregnancies demonstrate similar levels of mosaicism (12% vs 6.3%).
Retrograde Manual Lymphatic Drainage following Vascularized Lymph Node Transfer to Distal Recipient Sites for Extremity Lymphedema: A Retrospective Study and Literature Review
Authors: Roka-Palkovits Julia , Lin Miffy Chia-Yu , Tzou Chieh-Han J. , Tinhofer Ines , Cheng Ming-Huei
Published: August 2021

Background:

Vascularized lymph node transfer is an efficacious treatment for extremity lymphedema. This study investigated the outcome of retrograde manual lymphatic drainage for vascularized lymph node transfer to distal recipient sites.

Methods:

Lymphedema patients who underwent either complete decongestive therapy or vascularized lymph node transfer between 2013 and 2018 were retrospectively included. Retrograde manual lymphatic drainage was started with intermittent manual compression and the assistance of a sphygmomanometer and proximal-to-distal massage of the limb 1 month postoperatively. Outcomes evaluations used the circumferential reduction rate and the Lymphedema-Specific Quality-of-Life Questionnaire. Outcomes of vascularized lymph node transfer to proximal versus distal recipient sites in the literature between 2006 and 2018 were also compared.

Results:

One hundred thirty-eight unilateral extremity lymphedema patients, including 68 patients in the complete decongestive therapy group and 70 patients in the vascularized lymph node transfer group, were included. The mean circumferential reduction rate of 38.9 ± 2.5 percent in the vascularized lymph node transfer group was statistically greater than the 13.2 ± 10.1 percent rate in the complete decongestive therapy group (p = 0.01). At a mean follow-up of 36 months, the improvement of overall Lymphedema-Specific Quality-of-Life Questionnaire score from 3.8 ± 0.3 to 7.5 ± 1.8 in the vascularized lymph node transfer group was statistically greater than that in the complete decongestive therapy group (from 4.7 ± 0.9 to 5.0 ± 1.9; p < 0.01). In total, 536 lymphedema patients who underwent 548 vascularized lymph node transfers in 23 published articles were reviewed; the distal recipient-site group was found to have more efficacious results than the proximal recipient-site group.

Conclusion:

Vascularized lymph node transfer to a distal recipient site with standard retrograde manual lymphatic drainage significantly improved circumferential reduction rates and Lymphedema-Specific Quality-of-Life Questionnaire scores.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Rodeo Thumb: To Replant or Not
Authors: Davis Justin J. , Meade Anna E. , Cochran Lindsey , Sammer Douglas M. , Zhang Andrew Y.
Published: August 2021

Background:

This study investigated patient-reported outcomes after surgical treatment of rodeo thumb amputation to guide clinical decision-making.

Methods:

A retrospective review was performed for rodeo thumb amputations from 2009 to 2019. Patient-reported outcomes were collected and compared by injury level, age, and treatment. Two-sided t test was used to compare continuous variables, and Pearson chi-square test was used to compare categorical data.

Results:

The study included 37 patients. Patients with interphalangeal injuries treated with replantation had Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores similar to those treated with amputation (1 versus 8; p = 0.07). There was no significant difference in percentage of patients with similar or better roping ability after treatment (40 percent versus 79 percent; p = 0.26), and similar percentages were satisfied (80 percent versus 71 percent; p = 1.00). Patients with metacarpophalangeal injuries treated with replantation and those treated with amputation had similar questionnaire scores (7 versus 10; p = 0.47). Both groups had similar roping ability after treatment (67 percent versus 56 percent; p = 1.00), and there was no statistically significant difference in satisfaction (79 percent versus 44 percent; p = 0.34). Pediatric patients had questionnaire scores similar to those of adults (6 versus 8; p = 0.42). A significantly higher percentage of pediatric patients had similar roping ability following injury than adults (100 percent versus 54 percent; p = 0.02). Most patients in both groups were satisfied (89 percent versus 61 percent; p = 0.22).

Conclusions:

For both interphalangeal and metacarpophalangeal injuries, patient-reported outcomes were similar regardless of treatment. Children were able to return to roping and perform at a similar or higher level at a greater rate than adults, but had similar questionnaire scores and satisfaction.
Philanthropy in Plastic Surgery: Best Practices and Measuring Impact
Authors: McIntyre Joyce K. , Schoenbrunner Anna R. , Albert Rita A. , Gosman Amanda A.
Published: August 2021

Background:

Philanthropy in plastic surgery supports research, clinical care, academic infrastructure, and education in the United States and internationally. Plastic surgeons have opportunities to innovatively address unmet needs in their local and global communities by forming philanthropic nonprofit organizations.

Methods:

The authors queried three national philanthropic databases (Charity Navigator, Guidestar, and ProPublica) for Internal Revenue Service 990 form tax return information related to philanthropic plastic surgery organizations. The authors analyzed the financial information publicly available about current plastic surgery philanthropic organizations and their funding sources.

Results:

Seventy-three federally tax-exempt groups identified plastic surgery as their primary area of work to the Internal Revenue Service in 2019, and 52 of those organizations said they engaged in clinical and/or educational philanthropy.
3
In 2017, a total of $158.5 million was donated to these groups in cash and noncash donations including equipment and time. Analyses of 6 years (2013 to 2018) of tax records from groups that provide plastic surgery clinical, research, or educational philanthropy reveal that government grants provide very little funding for this work. Eighty-six percent of money raised for these groups in 2017 was collected by means of direct donations. Money obtained from fundraising events contributed 2 percent to their total monies raised in 2017 on average and 8 percent came from noncash gifts.

Conclusions:

A broad body of academic research is reviewed here that guides best practices and measuring a group’s impact and outcomes. The details of a philanthropic group’s organization and finances directly influence the impact of their work and, as such, are worthy of our sustained attention.
The Influence of Closing the Abdominal Donor-Site Superficial Fascial System in Deep Inferior Epigastric Perforator Flap Breast Reconstruction
Authors: Johnson Ariel C. , King Becky B. T. , Colakoglu Salih , Yang Jerry H. , Chong Tae W. , Mathes David W.
Published: August 2021

Background:

The superficial fascial system is routinely closed to alleviate tension at the abdominal donor site after harvest of the deep inferior epigastric artery perforator flap (DIEP) for breast reconstruction. This is thought to decrease rates of wound dehiscence and improve contour postoperatively. There has been no comparative analysis on closure of the superficial fascial system and its effect on donor-site outcomes.

Methods:

The authors retrospectively evaluated outcomes of DIEP flap breast reconstructions performed between 2017 and 2019. After May of 2018, the surgeons collectively agreed to stop closure of the superficial fascial system. All subsequent patients underwent closure of rectus abdominis fascia followed by skin closure. Patient demographic data and abdominal donor-site comorbidities were recorded between the superficial fascial system closure and no–superficial fascial system closure groups. Representative photographs of patients from the two groups were blindly assessed for scar appearance and contour using previously published grading scales. The results were compared.

Results:

DIEP flap breast reconstruction was performed in 103 consecutive women. Among patients with abdominal donor-site reconstruction, 66 had superficial fascial system closure and 37 did not. There was not a significant difference in fat necrosis or wound dehiscence between the two groups (p = 0.29 and p = 0.39, respectively). Postoperative abdominal scar and contour were evaluated by 10 independent raters and showed no significant difference between the two groups.

Conclusion:

Omission of superficial fascial system closure resulted in no difference in wound dehiscence or fat necrosis rates and aesthetic appearance of the abdominal scar and contour.

Clinical Question/Level of Evidence:

Therapeutic, III.
Thomas Henshaw's strange séance in Venice,
circa
1648: a coda to
Robert Boyle by himself and his friends
Authors: Hunter Michael
Published: August 2021

This article presents a hitherto unpublished account of a magical séance conducted by the virtuoso Thomas Henshaw (1618–1700), later Fellow of the Royal Society, while travelling in Venice
ca
1648. The episode had previously been known through an account of it given by Robert Boyle, but in Boyle's version its protagonist was unclear. It is now for the first time revealed as Henshaw on the basis of a further record of it among the papers of John Sharp, Archbishop of York (1645?–1714). The discrepancies between the ‘new’ version of the story and that given by Boyle are here elucidated and the opportunity is taken to outline the background to the séance in terms of the history of magic in early modern Venice. In addition, broader comments are included on the implications of the episode for attitudes towards alchemy and magic in the period.
Recovery of small plasmid sequences via Oxford Nanopore sequencing
Authors: Wick Ryan R. , Judd Louise M. , Wyres Kelly L. , Holt Kathryn E.
Published: August 2021

Oxford Nanopore Technologies (ONT) sequencing platforms currently offer two approaches to whole-genome native-DNA library preparation: ligation and rapid. In this study, we compared these two approaches for bacterial whole-genome sequencing, with a specific aim of assessing their ability to recover small plasmid sequences. To do so, we sequenced DNA from seven plasmid-rich bacterial isolates in three different ways: ONT ligation, ONT rapid and Illumina. Using the Illumina read depths to approximate true plasmid abundance, we found that small plasmids (<20 kbp) were underrepresented in ONT ligation read sets (by a mean factor of ~4) but were not underrepresented in ONT rapid read sets. This effect correlated with plasmid size, with the smallest plasmids being the most underrepresented in ONT ligation read sets. We also found lower rates of chimaeric reads in the rapid read sets relative to ligation read sets. These results show that when small plasmid recovery is important, ONT rapid library preparations are preferable to ligation-based protocols.
Transcriptional plasticity drives leukemia immune escape
Authors: Eagle Kenneth , Harada Taku , Kalfon Jérémie , Perez Monika W. , Heshmati Yaser , Ewers Jazmin , Koren Jošt Vrabič , Dempster Joshua M. , Kugener Guillaume , Paralkar Vikram R. , Lin Charles Y. , Dharia Neekesh V. , Stegmaier Kimberly , Orkin Stuart H. , Pimkin Maxim
Published: August 2021

Relapse of acute myeloid leukemia (AML) after allogeneic bone marrow transplantation (alloSCT) has been linked to immune evasion due to reduced expression of major histocompatibility complex class II (MHC-II) proteins through unknown mechanisms. We developed CORENODE, a computational algorithm for genome-wide transcription network decomposition, that identified the transcription factors (TFs) IRF8 and MEF2C as positive regulators and MYB and MEIS1 as negative regulators of MHC-II expression in AML cells. We show that reduced MHC-II expression at relapse is transcriptionally driven by combinatorial changes in the levels of these TFs, acting both independently and through the MHC-II coactivator CIITA. Beyond the MHC-II genes, MYB and IRF8 antagonistically regulate a broad genetic program responsible for cytokine signaling and T-cell stimulation that displays reduced expression at relapse. A small number of cells with altered TF levels and silenced MHC-II expression are present at the time of initial leukemia diagnosis, likely contributing to eventual relapse. Our findings reveal an adaptive transcriptional mechanism of AML evolution after allogenic transplantation whereby combinatorial fluctuations of TF levels under immune pressure result in selection of cells with a silenced T-cell stimulation program.
Procalcitonin to Predict Severity of Acute Cholangitis and Need for Urgent Biliary Decompression: Systematic Scoping Review
Authors: Silangcruz Krixie , Nishimura Yoshito , Czech Torrey , Kimura Nobuhiko , Yess James
Published: August 2021

Background

Serum Procalcitonin (PCT) has been reported as a potential biomarker to predict the severity of acute cholangitis (AC) or the need for urgent biliary decompression. This study aimed to identify and summarize the existing research about the serum PCT and the severity of AC, and to find gaps where future studies can be targeted towards.

Methods

Following the PRISMA Extension for Scoping Reviews, MEDLINE, EMBASE, and Google Scholar were searched for all peer-reviewed articles with relevant keywords including “cholangitis” and “procalcitonin” from their inception to July 13, 2021.

Results

We identified six studies. All the studies employed case-control design and aimed to evaluate the usefulness of serum PCT to predict the severity of AC with key identified outcomes. While potential cut-off values of serum PCT for severe AC ranged from 1.8–3.1 ng/mL, studies used different severity criteria and the definition of urgent biliary decompression. No studies proposed cut-off PCT values for the need for urgent biliary decompression.

Conclusion

This scoping review identified that the current level of evidence regarding the usefulness of serum PCT in assessing the severity of AC. Further clinical research is warranted with a focus on standardized outcome measures employing prospective or experimental designs.
Structural mechanism underpinning Thermus oshimai Pif1-mediated G-quadruplex unfolding
Authors: Dai Yang-Xue , Guo Hai-Lei , Liu Na-Nv , Chen Wei-Fei , Rety Stephane , Xi Xu-Guang
Published: August 2021

G-quadruplexes (G4s) are unusual DNA structures and can stall DNA replication, causing genomic instability for the cell. Although the solved crystal structure of the DHX36 helicase demonstrated that G4 was specifically targeted by a DHX36-specific motif (DSM), lack of complete structural details for general G4-resolving helicases without specific target motifs remains a barrier to the complete understanding of the molecular basis underlying the recognition and unfolding of G4s. Herein, we present the first X-ray crystal structure of the Thermus oshimai Pif1 (ToPif) complexed with a G4, thereby mimicking the physiological G4 formed during DNA replication. Strictly different from the previous determined G4-helicase structure of DHX36, our structure revealed that ToPif1 recognizes the entire native G4 via a cluster of amino acids at domains 1B/2B constituting a G4-Recognizing Surface (GRS). The overall topology of the G4 structure solved in this work maintains its three-layered propeller-type G4 topology, with no significant reorganization of G-tetrads upon protein binding. The three G-tetrads in G4 were differentially recognized by GRS residues mainly through electrostatic, ionic interactions and hydrogen bonds formed between the GRS residues and the ribose-phosphate backbone. Our structure explains how helicases from distinct superfamilies adopt different strategies for recognizing and unfolding G4s.
A dynamic rhizosphere interplay between tree roots and soil bacteria under drought stress
Authors: Oppenheimer-Shaanan Yaara , Jakoby Gilad , Starr Maya Laurencia , Karliner Romiel , Eilon Gal , Itkin Maxim , Malitsky Sergey , Klein Tamir
Published: August 2021

Root exudates are thought to play an important role in plant-microbial interactions. In return for nutrition, soil bacteria can increase the bioavailability of soil minerals. However, root exudates typically decrease in situations such as drought, calling into question the efficacy of bacteria-dependent mineral uptake in such stress.

Here we tested the hypothesis of exudate-driven microbial priming on Cupressus saplings grown in forest soil in custom-made rhizotron boxes. A 1-month imposed drought and concomitant inoculations with Bacillus subtilis and Pseudomonas stutzeri, bacteria species isolated from the forest soil, were applied using factorial design.

Direct bacteria counts and visualization by confocal microscopy showed that both bacteria associated with Cupressus roots. Interestingly, root exudation rates increased with bacteria under drought. Forty four metabolites in exudates were significantly different in concentration between irrigated and drought trees, including phenolic acid compounds and quinate, that were shown to be used as carbon and nitrogen sources by both bacterial species. Importantly, soil phosphorous bioavailability was maintained only in inoculated trees, mitigating drought-induced decrease in leaf phosphorus and iron.

Our observations of increased root exudation rate when drought and inoculation regimes were combined, support the idea of root recruitment of beneficial bacteria.
Nucleosome positioning on large tandem DNA repeats of the ‘601’ sequence engineered in Saccharomyces cerevisiae
Authors: Lancrey Astrid , Joubert Alexandra , Duvernois-Berthet Evelyne , Routhier Etienne , Raj Saurabh , Thierry Agnès , Sigarteu Marta , Ponger Loic , Croquette Vincent , Mozziconacci Julien , Boulé Jean-Baptiste
Published: August 2021

The so-called 601 DNA sequence is often used to constrain the position of nucleosomes on a DNA molecule in vitro. Although the ability of the 147 base pair sequence to precisely position a nucleosome in vitro is well documented, in vivo application of this property has been explored only in a few studies and yielded contradictory conclusions. Our goal in the present study was to test the ability of the 601 sequence to dictate nucleosome positioning in Saccharomyces cerevisiae in the context of a long tandem repeat array inserted in a yeast chromosome. We engineered such arrays with three different repeat size, namely 167, 197 and 237 base pairs. Although our arrays are able to position nucleosomes in vitro as expected, analysis of nucleosome occupancy on these arrays in vivo revealed that nucleosomes are not preferentially positioned as expected on the 601-core sequence along the repeats and that the measured nucleosome repeat length does not correspond to the one expected by design. Altogether our results demonstrate that the rules defining nucleosome positions on this DNA sequence in vitro are not valid in vivo, at least in this chromosomal context, questioning the relevance of using the 601 sequence in vivo to achieve precise nucleosome positioning on designer synthetic DNA sequences.
Multi-resolution electron spectrometer array for future free-electron laser experiments
Authors: Walter Peter , Kamalov Andrei , Gatton Averell , Driver Taran , Bhogadi Dileep , Castagna Jean-Charles , Cheng Xianchao , Shi Hongliang , Obaid Razib , Cryan James , Helml Wolfram , Ilchen Markus , Coffee Ryan N.
Published: August 2021

The design of an angular array of electron time-of-flight (eToF) spectrometers is reported, intended for non-invasive spectral, temporal, and polarization characterization of single shots of high-repetition rate, quasi-continuous, short-wavelength free-electron lasers (FELs) such as the LCLS II at SLAC. This array also enables angle-resolved, high-resolution eToF spectroscopy to address a variety of scientific questions on ultrafast and nonlinear light–matter interactions at FELs. The presented device is specifically designed for the time-resolved atomic, molecular and optical science endstation (TMO) at LCLS II. In its final version, the spectrometer comprises up to 20 eToF spectrometers aligned to collect electrons from the interaction point, which is defined by the intersection of the incoming FEL radiation and a gaseous target. The full composition involves 16 spectrometers forming a circular equiangular array in the plane normal to the X-ray propagation and four spectrometers at 54.7° angle relative to the principle linear X-ray polarization axis with orientations in the forward and backward direction of the light propagation. The spectrometers are capable of independent and minimally chromatic electrostatic lensing and retardation, in order to enable simultaneous angle-resolved photo- and Auger–Meitner electron spectroscopy with high energy resolution. They are designed to ensure an energy resolution of 0.25 eV across an energy window of up to 75 eV, which can be individually centered via the adjustable retardation to cover the full range of electron kinetic energies relevant to soft X-ray methods, 0–2 keV. The full spectrometer array will enable non-invasive and online spectral-polarimetry measurements, polarization-sensitive attoclock spectroscopy for characterizing the full time–energy structure of SASE or seeded LCLS II pulses, and support emerging trends in molecular-frame spectroscopy measurements.