bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic mouse model with postnatalNf1andp53loss recapitulates the histology and transcriptome of human malignant peripheral nerve sheath tumor
Authors: Inoue Akira , Janke Laura J , Gudenas Brian L , Jin Hongjian , Fan Yiping , Paré Joshua , Clay Michael R , Northcott Paul A , Hirbe Angela C , Cao Xinwei
Published: September 2021

Background

Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of NF1 and cooperating tumor suppressors, including CDKN2A/B, PRC2, and p53, is found in most MPNST. Inactivation of LATS1/2 of the Hippo pathway was recently shown to cause tumors resembling MPNST histologically, although Hippo pathway mutations are rarely found in MPNST. Because existing genetically engineered mouse (GEM) models of MPNST do not recapitulate some of the key genetic features of human MPNST, we aimed to establish a GEM-MPNST model that recapitulated the human disease genetically, histologically, and molecularly.

Methods

We combined 2 genetically modified alleles, an Nf1;Trp53 cis-conditional allele and an inducible Plp-CreER allele (NP-Plp), to model the somatic, possibly postnatal, mutational events in human MPNST. We also generated conditional Lats1;Lats2 knockout mice. We performed histopathologic analyses of mouse MPNST models and transcriptomic comparison of mouse models and human nerve sheath tumors.

Results

Postnatal Nf1;Trp53 cis-deletion resulted in GEM-MPNST that were histologically more similar to human MPNST than the widely used germline Nf1;Trp53 cis-heterozygous (NPcis) model and showed partial loss of H3K27me3. At the transcriptome level, Nf1;p53-driven GEM-MPNST were distinct from Lats-driven GEM-MPNST and resembled human MPNST more closely than do Lats-driven tumors.

Conclusions

The NP-Plp model recapitulates human MPNST genetically, histologically, and molecularly.
The repair of topoisomerase 2 cleavage complexes in Arabidopsis
Authors: Hacker Leonie , Dorn Annika , Enderle Janina , Puchta Holger
Published: September 2021

DNA–protein crosslinks (DPCs) and DNA double-stranded breaks (DSBs), including those produced by stalled topoisomerase 2 cleavage complexes (TOP2ccs), must be repaired to ensure genome stability. The basic mechanisms of TOP2cc repair have been characterized in other eukaryotes, but we lack information for plants. Using CRISPR/Cas-induced mutants, we show that Arabidopsis thaliana has two main TOP2cc repair pathways: one is defined by TYROSYL-DNA-PHOSPHODIESTERASE 2 (TDP2), which hydrolyzes TOP2–DNA linkages, the other by the DNA-dependent protease WSS1A (a homolog of human SPARTAN/yeast weak suppressor of smt3 [Wss1]), which also functions in DPC repair. TDP1 and TDP2 function nonredundantly in TOP1cc repair, indicating that they act specifically on their respective stalled cleavage complexes. The nuclease METHYL METHANESULFONATE AND UV-SENSITIVE PROTEIN 81 (MUS81) plays a major role in global DPC repair and a minor role in TOP2cc repair. DSBs arise as intermediates of TOP2cc repair and are repaired by classical and alternative nonhomologous end joining (NHEJ) pathways. Double-mutant analysis indicates that “clean” DNA ends caused by TDP2 hydrolysis are mainly religated by classical NHEJ, which helps avoid mutation. In contrast, the mutagenic alternative NHEJ pathway mainly processes nonligateable DNA ends. Thus, TDP2 promotes maintenance of plant genome integrity by error-free repair of TOP2cc.
Using the PODCI to Measure Motor Function and Parent Expectations in Children With Cerebral Palsy
Authors: Scott Kimberley S , Barbosa Gardenia O , Pan Jeff , Heathcock Jill C
Published: September 2021

Objective

Involving parents in the evaluation of their child with cerebral palsy (CP) is associated with enhanced neurodevelopmental outcomes. The pediatric outcomes data collection instrument (PODCI) is a patient-reported outcome measure primarily used to assess motor function following orthopedic surgical intervention or for older children with more independent motor function. The PODCI expectations scale has infrequently been reported in previous studies. This study aims to determine the relationship between parent-reported motor performance using the PODCI and motor capacity assessed by pediatric therapists for young children with CP across all ability levels and to explore the use of the PODCI expectations scale for quantifying therapy-related parent expectations.

Methods

This prospective cohort study included 108 participants with CP, 2 to 8 years of age, gross motor function classification systems (GMFCS) levels I to V. Measures included the PODCI, gross motor function measure (GMFM), and GMFCS.

Results

There were moderate (r = 0.513) to large (r = 0.885) relationships between PODCI and GMFM scores. PODCI scores were significantly different across GMFCS levels. Weak, significant relationships (r = −0.28) were found between function expectations scores and measures of function.

Conclusion

The PODCI, GMFM, and GMFCS provide different, but strongly related, information about the abilities of young children. The GMFM measures motor capacity. Parents report daily function and health-related quality of life for their child using the PODCI. Parent expectations for intervention outcomes may relate to a child’s motor function.

Impact

These study results are consistent with those for older children with greater independent mobility, indicating an opportunity for expanded use of the PODCI for measuring motor performance for younger children with CP across all ability levels. A strategy is provided for using the PODCI expectations scale to quantify parent therapy-related expectations in future research and clinical settings. Therapy-related expectations may relate to child outcomes.
Molecular Mechanism & Structure—Zooming in on Plant Immunity
Authors: Margets Alexandra , Rima Sharmin , Helm Matthew , Carter Morgan
Published: September 2021

The first of three International Society for Molecular Plant–Microbe Interactions (IS-MPMI) eSymposia was convened on 12 and 13 July 2021, with the theme “Molecular Mechanism & Structure—Zooming in on Plant Immunity”. Hosted by Jian-Min Zhou (Beijing, China) and Jane Parker (Cologne, Germany), the eSymposium centered on “Top 10 Unanswered Questions in MPMI” number five: Does effector-triggered immunity (ETI) potentiate and restore pattern-triggered immunity (PTI)—or is there really a binary distinction between ETI and PTI? Since the previous International Congress of IS-MPMI in 2019, substantial progress has been made in untangling the complex signaling underlying plant immunity, including a greater understanding of the structure and function of key proteins. A clear need emerged for the MPMI community to come together virtually to share new knowledge around plant immunity. Over the course of two synchronous, half days of programming, participants from 32 countries attended two plenary sessions with engaging panel discussions and networked through interactive hours and poster breakout rooms. In this report, we summarize the concerted effort by multiple laboratories to study the molecular mechanisms underlying ETI and PTI, highlighting the essential role of plant resistosomes in the formation of calcium channels during an immune response. We conclude our report by forming new questions about how overlapping signaling mechanisms are controlled.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Distribution of G143A Mutations Conferring Fungicide Resistance in Virginia Populations of Parastagonospora nodorum Infecting Wheat
Authors: Kaur Navjot , Mehl Hillary L.
Published: September 2021

Stagonospora nodorum blotch (SNB) caused by Parastagonospora nodorum is an important leaf spot disease in the mid-Atlantic United States. Disease management approaches include use of resistant varieties, cultural control, and foliar fungicides. Frequent use of foliar fungicides can select for fungicide resistance within pathogen populations. Recently, the first report of quinone outside inhibitor (QoI) fungicide resistance in the United States was made based on a relatively small collection of P. nodorum isolates from Virginia. The objective of this study was to conduct a statewide, 2-year survey of P. nodorum populations in Virginia wheat and quantify frequencies of the target-site mutation that confers QoI resistance. A total of 318 isolates of P. nodorum were obtained from wheat collected at seven locations distributed throughout the wheat-growing regions of Virginia in 2018 and 2019. A previously designed pyrosequencing assay that detects the G143A substitution in the cytochrome b gene of P. nodorum was used to screen isolates for the presence or absence of the target site mutation. The G143A substitution was detected in all sampled fields. Among locations and years, frequencies of the mutation in P. nodorum populations ranged from 5 to 32% (mean = 19%). Thus, the QoI-resistance-conferring G143A mutation was widespread in P. nodorum populations in Virginia, and it occurred at a relatively high frequency. Results suggest that fungicides containing QoI active ingredients may not be effective for controlling SNB in Virginia and the surrounding region, and application of standalone QoI fungicides for disease control in wheat is not recommended.
Comparative Analysis of Infection Process in Pima Cotton Differing in Resistance to Fusarium Wilt Caused byFusarium oxysporumf. sp.vasinfectumRace 4
Authors: Zhu Yi , Abdelraheem Abdelraheem , Cooke Peter , Wheeler Terry , Dever Jane K. , Wedegaertner Tom , Hake Kater , Zhang Jinfa
Published: September 2021

Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4) causes an early season cotton disease including seedling deaths. This study compared two Pima cottons (Gossypium barbadense) in the infection process of FOV4 using a confocal and a scanning electron microscope. Seedlings were grown in a hydroponic system and inoculated with a virulent local FOV4 isolate. As compared with the susceptible Pima S-7, the resistant Pima PHY 841 RF had significantly fewer conidia attached and germinated on the root surface. FOV4 penetration into the root epidermis of PHY 841 RF was delayed until 24 h postinoculation (hpi) as compared with 8 hpi in Pima S-7. In Pima S-7, hyphae progressed to the xylem through the cortex between 5 and 7 days postinoculation. However, hyphae grew much slower in the cortex with no apparent hyphae observed in the xylem of PHY 841 RF. At plant maturity, no FOV4 was detected through fungal isolation and PCR in the stem of PHY 841 RF and its resistance donor parents PHY 800 and Pima S-6, as compared with Pima S-7 and DP 744 with positive results. The results demonstrate that PHY 841 RF is resistant to FOV4, due to delayed infection, reduced fungal growth and reproduction, and prevention of the fungus from invading the xylem.
Advances in Hemostatic Wound Dressings: Clinical Implications and Insight
Authors: Agarwal Roopali , Niezgoda Jonathan , Niezgoda Jeffrey , Madetipati Nethaji , Gopalakrishnan Sandeep
Published: September 2021

Hemorrhagic shock is one of the leading causes of prehospital death in the armed forces. In this state, the body begins to shut down because of blood volume depletion. In both civilian and military trauma, a significant number of hemorrhage deaths occur in the first several hours after injury. Researchers all over the globe are working to develop relatively inexpensive and easy-to-transport products to prevent soldiers from going into hemorrhagic shock. For example, many advances have been made during the last several years toward the development of ideal hemostatic dressings. No current hemostatic agents meet all of the requirements, but the ideal dressing would fulfill many important measures: minimizes or stops blood flow within minutes, contains hemostatic agents to enhance blood clotting, is easy to apply, does not need preapplication preparation, has a reasonably long shelf life, is safe to use, prevents bacterial or viral transmission, is stable at extreme temperatures, and is inexpensive.

 For this literature review, the authors conducted an extensive search of academic scientific databases for relevant keywords and assessed and summarized the results. This review aimed to identify recent advances in hemostatic wound dressings; summarize the currently available dressings and their supporting literature; and discuss the compositions, mechanisms of action, and clinical relevance of each category of dressing. In addition, case studies and suggestions for future research into hemorrhage control with new hemostatic agents are provided.
Evaluation of an Initiative to Decrease the Use of Oxygen Supplementation for Category II Fetal Heart Rate Tracings
Authors: Burd Julia E. , Anderson Kathryn , Berghella Vincenzo , Duncan Daniel G. , Baxter Jason K. , Quist-Nelson Johanna
Published: September 2021

OBJECTIVE:

To examine compliance with a guideline to reduce exposure to supplemental oxygen for category II fetal heart rate (FHR) tracings in normally oxygenated laboring patients.

METHODS:

All patients in labor in an urban academic medical center from January 1 to July 31, 2020 were assessed. The preintervention group included those who delivered from January 1 to March 19, 2020. On March 20, 2020, a new guideline took effect that recommended no maternal supplemental oxygen for category II FHR tracings. The postintervention group delivered from March 20 to July 31, 2020. Exclusion criteria were planned cesarean delivery, multiple gestations, delivery at less than 24 weeks of gestation, intrauterine fetal death, and patients who received supplemental oxygen for an oxygen saturation lower than 95%. The primary outcome was the percentage of patients who received oxygen in labor analyzed by control charts and the rules of special cause variation. Chi-squared and t tests were used for secondary outcome assessment. P<.05 was considered significant.

RESULTS:

A total of 1,333 patients were included, 474 patients in the preintervention group and 859 in the postintervention group. Oxygen was administered to 22.6% of patients before guideline implementation, compared with 0.6% after the guideline. Special cause variation was detected with an 8-point shift starting the month that the guideline was implemented, indicating statistical significance. There were no differences in any studied secondary maternal or fetal outcomes, although our statistical power to detect differences in infrequent outcomes was limited.

CONCLUSION:

This quality-improvement study demonstrated significant adherence to the guideline that supplemental oxygen would no longer be given to patients with category II FHR tracings in the absence of maternal hypoxemia, with no significant change in maternal or perinatal outcomes.
Pro-pigmentary action of 5-fluorouracil through the stimulated secretion of CXCL12 by dermal fibroblasts
Authors: Liao Zhi-Kai , Hu Shuang-Hai , Han Bin-Yu , Qiu Xie , Jiang Shan , Lei Tie-Chi
Published: September 2021

Background:

There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.

Methods:

We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes.

Results:

Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100).

Conclusion:

5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.
Computed tomography-identified phenotypes of small airway obstructions in chronic obstructive pulmonary disease
Authors: Li Tao , Zhou Hao-Peng , Zhou Zhi-Jun , Guo Li-Quan , Zhou Linfu
Published: September 2021

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characteristic of small airway inflammation, obstruction, and emphysema. It is well known that spirometry alone cannot differentiate each separate component. Computed tomography (CT) is widely used to determine the extent of emphysema and small airway involvement in COPD. Compared with the pulmonary function test, small airway CT phenotypes can accurately reflect disease severity in patients with COPD, which is conducive to improving the prognosis of this disease. CT measurement of central airway morphology has been applied in clinical, epidemiologic, and genetic investigations as an inference of the presence and severity of small airway disease. This review will focus on presenting the current knowledge and methodologies in chest CT that aid in identifying discrete COPD phenotypes.
A Case of in utero Transmission of Drug-resistant HIV in the United States
Authors: Weyland Cassie , Mirani Gayatri , Gillespie Susan L. , Paul Mary E.
Published: September 2021

Thanks to the development of antiretroviral drugs and the implementation of routine perinatal prophylaxis, primarily containing zidovudine, modern-day rates of perinatal transmission of HIV are very low in developed countries. We present a case of perinatal transmission of HIV with extensive nucleoside reverse transcriptase inhibitor resistance as a reminder that perinatal transmission of resistance mutations can occur. This case calls for further investigation into the utility of using genotype to determine neonatal prophylaxis in the setting of maternal HIV drug resistance.
Prevalence of Latent Tuberculosis Infection Among Healthy Young Children and Adolescents and a Two-step Approach for the Diagnosis of Tuberculosis Infection in Chengdu, China
Authors: Jia Jihang , Chen Dapeng , Liu Li , Siddiqui Mohd Jaish , Yang Fan , Zhu Yu , Liao Qiong , Luo Shuanghong , Shu Min , Wen Yang , Gao Lihong , Li Xu , Long Lilin , Peng Xiaoshan , Li Weiran , Liu Yang , Xu Wanting , Han Qian , Wu Huaiyong , Guo Jiarong , Du Xi , Guo Qin , Wan Chaomin
Published: September 2021

Background:

China has a high burden of tuberculosis and latent tuberculosis infection (LTBI). The aim of this study was to estimate the prevalence of LTBI among healthy young children and adolescents and test a 2-step approach to explore the threshold for the diagnosis of tuberculosis infection in Chengdu, China.

Methods:

Healthy preschool children and school-going children in Chengdu, Sichuan Province, were screened for LTBI using the tuberculin skin test (TST). Preschool children with TST ≥ 5 mm also underwent interferon-γ release assay (IGRA) to explore the threshold of this 2-step approach.

Results:

In total, 5667 healthy young children and adolescents completed TST test between July 2020 and January 2021 and were included in the present analysis. The age of the participants ranged from 2.4 to 18 years (median 7.25 ± 4.514 years), of which 2093 (36.9%) were younger than 5 years. The overall prevalence of LTBI was 6.37% and 6.64% in children younger than 5 years old. Fourteen of the 341 preschool children with TST ≥5 mm were interferon-γ release assay positive, of which 4 showed a TST result of 5–10 mm, and 6 preschool children received preventive treatment for LTBI.

Conclusions:

Healthy young children and adolescents should also be considered as important target populations for LTBI screening. TST can be recommended for first-line screening as part of a 2-step approach for LTBI screening using a positive threshold of 5 mm.
Aerosol Generation During Bronchoscopy
Authors: Reddy Chakravarthy , Sethi Jaskaran , Balwan Akshu , Iravani Aidin , Ansari Sikandar , Kelly Kerry
Published: September 2021

Background:

Bronchoscopy is an aerosol-generating procedure and can place the health care providers at risk for exposure to viral pathogens. The pattern of aerosol generation during  different aspects of bronchoscopy are poorly understood. The goal of this study is to characterize the pattern of aerosol generation during flexible and rigid bronchoscopy performed under moderate sedation or general anesthesia (GA). The inhalable mass concentration of aerosol generated during the procedures was measured continuously.

Methods:

The aerosol concentration in the endoscopy room at baseline and while the procedures were performed was measured. Procedures included flexible bronchoscopies with moderate sedation, flexible bronchoscopies performed through endotracheal tube under GA and rigid bronchoscopies under GA. Changes from the baseline were measured continuously during the bronchoscopy.

Results:

Measurements obtained during the procedure were compared with the baseline reading. For flexible bronchoscopy under moderate sedation, the inhalable aerosol fraction was significantly higher (P=0.036) during atomization of lidocaine. For Flexible bronchoscopy through endotracheal tube, inhalable aerosol fraction was significantly higher (P<0.001) during intubation and extubation. For rigid bronchoscopy done under GA with jet ventilation, inhalable aerosol fraction was significantly higher during both the bronchoscopy (P=0.01) and recovery (P=0.012).

Conclusion:

Elevated levels of aerosol were generated during all aspects of bronchoscopy. However, atomization of lidocaine, intubation, extubation, and recovery generated the most aerosol.
Diagnostic value of combined serological markers in the detection of acute cerebral infarction
Authors: Zhao Xiaowen , Zhao Min , Pang Baojun , Zhu Yingnan , Liu Jizhu
Published: September 2021

To evaluate the value of the combination schemes of 10 serological markers in the clinical diagnosis of acute cerebral infarction.

The level of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, homocysteine (HCY), lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were analyzed in 154 patients with acute ischemic cerebral infarction. The optimized diagnostic combination for acute cerebral infarction was explored by calculating the maximum area under the receiver operating characteristic curves (AUC).

The levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, HCY, lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were significantly higher in the patient vs the control group. Moreover, the positive rate of HCY reached 89.9%. The analysis of the receiver operating characteristic curve of each index and their combinations showed that the minimum AUC of HDL-C alone was 0.543, while the maximum AUC of HCY was 0.853. A multiple logistic regression analysis indicated that HDL-C was a slightly significant variate in the diagnosis of acute cerebral infarction.

The value of individual serological markers in the diagnosis of acute cerebral infarction was slightly significant, while the combination of the markers significantly improved the efficiency of its diagnosis.
Postoperative complications observed with robotic versus laparoscopic surgery for the treatment of rectal cancer
Authors: Liu Chengkui , Li Xiaoqing , Wang Qingfeng
Published: September 2021

Background:

This is an updated meta-analysis comparing the postoperative complications observed with robotic versus laparoscopic surgery (LS) for the treatment of rectal cancer.

Methods:

Cochrane central, MEDLNE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica dataBASE), Google Scholar, Web of Science and http://www.ClinicalTrials.gov were searched for studies (published after the year 2015), comparing robotic versus LS for the treatment of rectal cancer. The postoperative outcomes were considered as the endpoints in this analysis. RevMan 5.4 was used to carry out the statistical analysis. Risk ratio (RR) with 95% confidence intervals (CI) were used to represent the results following data analysis.

Results

A total number of 22,744 participants were included in this study whereby 9178 participants were assigned to the robotic surgery and 13,566 participants were assigned to the LS group. The time period of patients’ enrollment varied from years 2007 to 2017. Our results showed that overall complications (RR: 0.91, 95% CI: 0.71–1.17; P = .45), wound complications (RR: 0.81, 95% CI: 0.64–1.04; P = .09), anastomotic leak (RR: 1.12, 95% CI: 0.88–1.42; P = .37), anastomotic bleeding (RR: 0.88, 95% CI: 0.29–2.64; P = .82), stoma-related complications (RR: 0.88, 95% CI: 0.24–3.21; P = .85), intra-abdominal abscess (RR: 0.53. 95% CI: 0.22–1.31; P = .17), urinary tract infection (RR: 0.94, 95% CI: 0.53–1.66; P = .83), enterocolitis (RR: 1.35, 95% CI: 0.38–4.71; P = .64), reoperation (RR: 0.85, 95% CI: 0.46–1.54; P = .58), and mortality (RR: 0.75, 95% CI: 0.34–1.62; P = .46) were not significantly different between robotic-assisted versus LS for rectal cancer. Postoperative ileus (RR: 1.21, 95% CI: 0.81–1.81; P = .34), readmission (RR: 1.17, 95% CI: 0.75–1.83; P = .48), and urinary retention (RR: 0.51, 95% CI: 0.21–1.23; P = .14) were also similarly manifested.

Conclusions:

In this updated meta-analysis, both robotic and laparoscopic surgeries were equally effective for the treatment of rectal cancer. Similar postoperative complications were observed. However, our analysis was restricted only to postoperative outcomes, parameters such as duration of surgery were not taken into consideration.
Robotic sacrocolpopexy in pelvic organ prolapse: a review of current literature
Authors: Pushkar Dmitry Y. , Kasyan George R. , Popov Alexander A.
Published: September 2021

Purpose of review

Recently, robotic sacrocolpopexy has become the gold standard for treating genital prolapse. Despite this, there is still much interest in this procedure, and many questions remain unanswered. This review focuses on the most critical articles on this issue that have been published in the last 2 years.

Recent findings

A summary of 23 articles is provided. There were no differences in total postoperative complications, postoperative stress incontinence, mesh erosion, and the success of the two surgical techniques in long-term investigations. Obesity modestly increases robotic approach difficulty and does not raise the mesh erosion rate or prolapse recurrence rate. Ultra-light and preprepared meshes with alternative fixation techniques can be applied with these procedures. Another emerging trend is alternative robotic approaches and the use of single-port surgery.

For women with pelvic organ prolapse, especially the elderly and obese, robotic sacrocolpopexy is well tolerated and effective. Despite highly restricted and heterogeneous data, recent investigations have included single incision methods and new mesh/fixation materials. Randomized trials with large sample size and excellent quality are necessary before the practical implementation of new techniques.
Symmetry Is Associated With Interlimb Coordination During Walking and Pedaling After Stroke
Authors: Cleland Brice T. , Schindler-Ivens Sheila
Published: September 2021

Background and Purpose:

Asymmetry during walking may be explained by impaired interlimb coordination. We examined these associations: (1) propulsive symmetry with interlimb coordination during walking, (2) work symmetry with interlimb coordination during pedaling, and (3) work symmetry and interlimb coordination with clinical impairment.

Methods:

Nineteen individuals with chronic stroke and 15 controls performed bilateral, lower limb pedaling with a conventional device and a device with a bisected crank and upstroke assistance. Individuals with stroke walked on a split-belt treadmill. Measures of symmetry (%Propulsionwalk, %Workped) and interlimb phase coordination index (PCIwalk, PCIped) were computed. Clinical evaluations were the lower extremity Fugl-Meyer (FMLE) and walking speed. Associations were assessed with Spearman's rank correlations.

Results:

Participants with stroke displayed asymmetry and impaired interlimb coordination compared with controls (P ≤ 0.001). There were significant correlations between asymmetry and impaired interlimb coordination (walking: R
2 = 0.79, P < 0.001; pedaling: R
2 = 0.62, P < 0.001) and between analogous measures across tasks (%Workped, %Propulsionwalk: R
2 = 0.41, P = 0.01; PCIped, PCIwalk: R
2 = 0.52, P = 0.003). Regardless of task, asymmetry and interlimb coordination were correlated with FMLE (R
2 ≥ 0.48, P ≤ 0.004) but not walking speed. There was larger within group variation for %Propulsionwalk than %Workped (Z = 2.6, P = 0.005) and for PCIped than PCIwalk (Z = 3.6, P = 0.003).

Discussion and Conclusions:

Pedaling may provide useful insights about walking, and impaired interlimb coordination may contribute to asymmetry in walking. Pedaling and walking provide distinct insights into stroke-related impairments, related to whether the task allows compensation (walking > pedaling) or compels paretic limb use (pedaling > walking). Pedaling a device with a bisected crank shaft may have therapeutic value.

Video Abstract available for more insight from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A365).
Providers PrEP: Identifying Primary Health care Providers' Biases as Barriers to Provision of Equitable PrEP Services
Authors: Hull Shawnika J. , Tessema Hanna , Thuku Jeri , Scott Rachel K.
Published: September 2021

Background:

Despite their disparately high HIV incidence and voiced willingness to use pre-exposure prophylaxis (PrEP), Black cisgender women's knowledge and uptake of PrEP are low, especially relative to White cisgender women and men who have sex with men. Mounting evidence demonstrates that health care provider recommendations are a critical factor in women's awareness, willingness, and ability to uptake PrEP. Health care providers may make clinical judgments about who is (not) a good candidate for PrEP based on unconscious and conscious stereotypes and prejudice.

Setting:

We conducted an online experiment among N = 160 health care providers with prescribing privileges in the 48 HIV hotspot counties.

Method:

Providers received 1 of 4 vignettes about a PrEP eligible woman. Vignettes varied by patient race and substance use status. Then, providers reported their willingness to discuss PrEP with the patient and willingness to prescribe PrEP to her.

Results:

We tested 2 models predicting providers (1) willingness to discuss and (2) willingness to prescribe PrEP, contingent on their racial attitudes. Providers who scored high on a modern racism measure were less willing to discuss and prescribe PrEP to the Black patient. These effects were mediated by provider perceptions of patients' abilities to adhere to PrEP, but not their expectations of risk compensatory behaviors.

Conclusions:

Our findings highlight the importance of applying an intersectional lens in documenting the processes that exacerbate inequities in PrEP use. This study provides evidence to support the development of interventions that address the mechanisms that work to thwart optimal care.
18F-FDG PET/CT of Malignant Presacral Masses in Currarino Syndrome
Authors: Nguyen Ba D.
Published: September 2021

The Currarino syndrome is characterized by 3 main features: anorectal malformation, presacral lesion, and dysgenesis of the sacrum and coccyx. The presacral lesion is usually benign with a rare occurrence of malignant degeneration. The author presents 2 cases of Currarino syndrome with presacral mucinous adenocarcinoma and neuroendocrine tumor depicted by 18F FDG PET/CT.
Malignant Lymphoma Diagnosed as Gallbladder Carcinoma on 18F-FDG PET/CT
Authors: Xu Lian , Yu Xiaofeng , Chen Yumei , Liu Jianjun
Published: September 2021

Extranodal primary lymphoma of gallbladder is extremely rare. We report a 48-year-old woman initially diagnosed as gallbladder carcinoma with lymph nodes metastases by contrast-enhanced CT and MRI. Meanwhile the images of 18F-FDG PET/CT highly suggested gallbladder carcinoma due to the necrosis in one of the enlarged lymph nodes. However, it was proved to be diffuse large B-cell lymphoma by the histopathological diagnosis.
Increased 68Ga-FAPI Activity in Malignant Melanoma of the Nasal Cavity
Authors: Ou Lei , Yang Xiao , Liu Huipan , Gong Weidong , Zhang Chunyin
Published: September 2021

We report the case of a 56-year-old man who presented with a 1-month history of recurrent right-sided epistaxis. Nasal endoscopy revealed a mass in the right nasal cavity, and CT scans showed a nasal space-occupying lesion. 68Ga-FAPI PET/CT demonstrated a high FAPI uptake of the mass in the right nasal cavity. Biopsy revealed a malignant melanoma.
123I Scintigraphy Mirror Image of Graves Disease Induced by Radioiodine Treatment for Toxic Adenoma
Authors: Lugat Alexandre , Drui Delphine , Bach-Ngohou Kalyane , Guillot Pascale , Mourrain-Langlois Emmanuelle , Kraeber-Bodéré Françoise , Ansquer Catherine
Published: September 2021

A 61-year-old woman presenting with hyperthyroidism received 131I therapy for a toxic adenoma diagnosed by 123I scintigraphy. Six months later, the patient had a relapse of hyperthyroidism, and 123I scintigraphy showed a mirror image of the first scintigraphy: a high and diffuse uptake in the thyroid gland except for the previously treated nodule. Graves disease was confirmed by elevated thyrotropin receptor antibodies. The patient was cured by a second radioiodine therapy. Radioiodine-induced Graves disease may occur within 6 months of 131I treatment of toxic adenoma and can be treated with a second line of 131I.
68Ga-FAPI PET/CT Imaging of Multiple Muscle Metastases of Pancreatic Cancer
Authors: Gong Weidong , Yang Xiao , Wu Junhao , Ou Lei , Zhang Chunyin
Published: September 2021

A 67-year-old man presented with generalized muscle pain for 2 months. A potential malignancy was suspected. The patient was subsequently enrolled in the clinical trial of 68Ga-FAPI. Increased activity of FAPI and FDG was observed in muscle lesions. Moreover, 68Ga-FAPI PET/CT showed intense FAPI uptake in the pancreas. Finally, pancreas and left iliopsoas muscle biopsies confirmed the diagnosis of pancreatic cancer with multiple muscle metastases.
Anti-microbial effect of filtered 222nm excimer lamps in a hospital waiting area
Authors: Thyrsted Jacob , Helbo Skaarup Søren , Fløe Hvass Andreas , Joensen Sara Moeslund , Nielsen Stine Y. , Bendstrup Elisabeth , Hauschildt Pernille , Holm Christian K.
Published: September 2021

Background

Hospital aquired infections is a considerable challenge for vulnerable patients. Ultraviolet light based on the excitation of mercury emit light at 254nm and has well established antimicrobial effects but the use hereof in populated areas is hindered by the carcinogenic properties of 254nm. This is in contrast to the recently developed excimer lamps based on krypton chloride (KrCl). These lamps emit light with a peak intensity at a wavelength of 222nm and have recently been demonstrated to have broad bactericidal and viricidal effects including efficient inactivation of SARS-CoV2. It is, however, unclear how efficiently 222nm lamps perform in a real-life setting such as a hospital waiting area. In this study we aimed to assess the antimicrobial efficacy of filtered 222nm excimer lamps in a real-world setting at an out-patient pulmonology clinic.

Methods

Filtered KrCl 222nm excimer lamps (UV222 lamps) were installed in a densely populated waiting room at the out-patient waiting area at Department of Respiratory Diseases and Allergy at Aarhus University Hospital, Aarhus, Denmark. Furniture sufaces were sampled and analyzed for bacterial load in a single arm interventional longitudinal study with and without exposure to filtered 222nm UVC-light. Furthermore, bacterial species were identified using MALDI-ToF mass-spectrometry.

Findings

The exposure to filtered 222nm UVC-light significantly reduced the number of colony-forming-units, and patches with high desity of bacteria. Pathogenic bacteria such as Staphylococcus Aureus and Staphylococcus Epidermidis were detected only in the non-exposed areas suggesting that these species are highly sensitive to inactivation by 222nm UVC-light.

Conclusion

Filtered 222nm UVC-light is highly anti-microbial in a real-world clinical setting reducing bacterial load and eradicating clinically relevant bacteria species. Filtered 222nm UVC-light has the potential to become an important part of current and future anti-microbial prevention in the clinic.
Network Meta-Analysis Comparing the Short and Long-Term Outcomes of Alternative Access for Transcatheter Aortic Valve Replacement
Authors: Ranka Sagar , Lahan Shubham , Chhatriwalla Adnan K. , Allen Keith B. , Verma Sadhika , Villablanca Pedro
Published: September 2021

Objectives

This study aimed to compare short- and long-term outcomes following various alternative access routes for transcatheter aortic valve replacement (TAVR).

Methods

Thirty-four studies with a pooled sample size of 30,986 records were selected by searching PubMed and Cochrane library databases from inception through 11thJune 2021 for patients undergoing TAVR via 1 of 6 different access sites: Transfemoral (TF), Transaortic (TAO), Transapical (TA), Transcarotid (TC), Transaxillary/Subclavian (TSA), and Transcaval (TCV). Data extracted from these studies were used to conduct a frequentist network meta-analysis with a random-effects model using TF access as a reference group.

Results

Compared with TF, both TAO [RR 1.91, 95% CI (1.46–2.50)] and TA access [RR 2.12, 95%CI (1.84–2.46)] were associated with an increased risk of 30-day mortality. No significant difference was observed for stroke, myocardial infarction, major bleeding, conversion to open surgery, and major adverse cardiovascular or cerebrovascular events in the short-term (≤ 30 days). Major vascular complications were lower in TA [RR 0.43, (95% CI, 0.28-0.67)] and TC [RR 0.51, 95% CI (0.35-0.73)] access compared to TF. The 1-year mortality was higher in the TAO [RR of 1.35, (95% CI, 1.01–1.81)] and TA [RR 1.44, (95% CI, 1.14–1.81)] groups.

Conclusion

Non-thoracic alternative access site utilization for TAVR implantation (TC, TSA and TCV) is associated with similar outcomes to conventional TF access. Thoracic TAVR access (TAO and TA) is associated with increased short and long-term mortality.
Neuromuscular risk factors for non-contact knee injury: a systematic review and meta-analysis
Authors: McGuire Bonar , King Ben
Published: September 2021

Objectives

Identify neuromuscular risk factors for non-contact knee injury, using a systematic review and meta-analysis, to inform the development of preventive strategies.

Methods

Medline, Web of Science and SCOPUS were searched from inception until November 2020. Prospective and nested case-control studies that analysed baseline neuromuscular characteristics as potential risk factors for subsequent non-contact knee injuries were included. Two reviewers independently appraised methodological quality using a modified Newcastle–Ottawa Scale. Meta-analysis was performed where appropriate, with standardised mean differences calculated for continuous scaled data.

Results

Seventeen studies were included, comprising baseline data from 5,584 participants and 415 non-contact knee injuries (heterogeneous incidence = 7.4%). Protocols and outcome measures differed across studies, limiting data pooling. Twenty-one neuromuscular variables were included in the meta-analysis. Three were identified as risk factors. For patellofemoral pain, among military recruits: reduced non-normalised quadriceps strength at 60º/s (SMD −0.66; 95% CI −0.99, −0.32); reduced quadriceps strength at 240º/s (normalised by body mass) (SMD −0.53; CI −0.87, −0.20). For PFP/ACL injury among female military recruits: reduced quadriceps strength at 60º/s (normalised by body mass) (SMD −0.50; CI −0.92, −0.08).

Conclusions

Quadriceps weakness is a risk factor for PFP among military recruits, and for PFP/ACL injury among female military recruits. However, the effect sizes are small, and the generalisability of these findings is limited. The effectiveness of quadriceps strengthening interventions for preventing PFP and ACL injury merits evaluation in prospective randomised trials.
Plotgardener: Cultivating precise multi-panel figures in R
Authors: Kramer Nicole E , Davis Eric S , Wenger Craig D , Deoudes Erika M , Parker Sarah M , Love Michael I , Phanstiel Douglas H
Published: September 2021

The R programming language is one of the most widely used programming languages for transforming raw genomic data sets into meaningful biological conclusions through analysis and visualization, which has been largely facilitated by infrastructure and tools developed by the Bioconductor project. However, existing plotting packages rely on relative positioning and sizing of plots, which is often sufficient for exploratory analysis but is poorly suited for the creation of publication-quality multi-panel images inherent to scientific manuscript preparation. We present plotgardener, a coordinate-based genomic data visualization package that offers a new paradigm for multi-plot figure generation in R. Plotgardener allows precise, programmatic control over the placement, aesthetics, and arrangements of plots while maximizing user experience through fast and memory-efficient data access, support for a wide variety of data and file types, and tight integration with the Bioconductor environment. Plotgardener also allows precise placement and sizing of ggplot2 plots, making it an invaluable tool for R users and data scientists from virtually any discipline.

Availability

Package:https://bioconductor.org/packages/plotgardener

Code:https://github.com/PhanstielLab/plotgardener

Documentation:https://phanstiellab.github.io/plotgardener/
Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes
Authors: Boukredine Axel , Saada Sofiane , Durand Stéphanie , Nivet Alexandre , Bessette Barbara , Rehailia Amel , Clavère Pierre , Jauberteau Marie-Odile , Deluche Elise , Lalloué Fabrice
Published: September 2021

Background

Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor during adulthood. One of the major treatments is the association of surgery and a combination of chemo and radiotherapies. Despite its immediate efficiency, it fails to prevent the cancer recurrence in the irradiated area due to radioresistance mechanisms.

MicroRNAs (miRNAs or miR) are small non-coding, single strand RNA molecules encoding to various specific genes and able to regulate their expression and induce the tumor cell survival leading to radioresistance. Small extracellular vesicles (EVs), or exosomes released by tumor cells in tumor microenvironment and blood circulation are able to transport and diffuse miRNAs and affect the microenvironment by spreading the miRNAs, which drive radioresistance.

Aims

To identify the variations of miRNAs expression induced by irradiation in human glioblastoma U87-MG cells and their secreted exosomes collected in supernatants.

To analyze the miRNAs variations in EVs-derived from the plasma of patients during radiotherapy, in order to identify a miRNA signature induced by radiotherapy in a liquid biopsy.

Materiel and methods

U87-MG cells were cultured on plates and exposed to irradiation. miRNAs analyzes were performed in cells and in EVs isolated from cell supernatants to determine miRNAs expressions both in cells and in secreted exosomes before and after irradiation.

Plasma-derived EVs were collected from 4 glioblastoma patients before and after surgery and radiotherapy treatments.

Conclusion

The analysis of miRNAs expression profiles in both GBM cells and their derived EVs revealed that miR profile changes after irradiation. However, the number of similar miR between cells or EVs, following cell irradiation, was restricted to 3 miRs alone suggesting that the irradiation-induced changes in the miR profile in the cells and their EVs are not closely linked. In this context, the miR profile in EVs from patients plasma was investigated to establish a potential link with the miRNAs profile observed in EVs from irradiated cells and to assess its relationship with the response to radiotherapy. Three miRs (different from those identified in cells) were common between EVs derived from cells and patients derived-exosomes. These miRs detected in circulating EVs could provide a specific and reliable signature in response to ionizing radiation, which could be useful for monitoring the effectiveness of radiotherapy. Further experiments on a larger patients population with clinical data could also help to define whether this signature might have a prognostic value on the response to radiotherapy.