bluuebunny/crossref_metadata_2025 huggingface dataset:
APE1 senses DNA single-strand breaks for repair and signaling
Authors: Lin Yunfeng , Raj Jude , Li Jia , Ha Anh , Hossain Md Akram , Richardson Christine , Mukherjee Pinku , Yan Shan
Published: December 2019

DNA single-strand breaks (SSBs) represent the most abundant type of DNA damage. Unrepaired SSBs impair DNA replication and transcription, leading to cancer and neurodegenerative disorders. Although PARP1 and XRCC1 are implicated in the SSB repair pathway, it remains unclear how SSB repair and SSB signaling pathways are coordinated and regulated. Using Xenopus egg extract and in vitro reconstitution systems, here we show that SSBs are first sensed by APE1 to initiate 3′–5′ SSB end resection, followed by APE2 recruitment to continue SSB end resection. Notably, APE1’s exonuclease activity is critical for SSB repair and SSB signaling pathways. An APE1 exonuclease-deficient mutant identified in somatic tissue from a cancer patient highlighted the significance of APE1 exonuclease activity in cancer etiology. In addition, APE1 interacts with APE2 and PCNA, although PCNA is dispensable for APE1’s exonuclease activity. Taken together, we propose a two-step APE1/APE2-mediated mechanism for SSB end resection that couples DNA damage response with SSB repair in a eukaryotic system.
The SINEB1 element in the long non-coding RNA Malat1 is necessary for TDP-43 proteostasis
Authors: Nguyen Tuan M , Kabotyanski Elena B , Reineke Lucas C , Shao Jiaofang , Xiong Feng , Lee Joo-Hyung , Dubrulle Julien , Johnson Hannah , Stossi Fabio , Tsoi Phoebe S , Choi Kyoung-Jae , Ellis Alexander G , Zhao Na , Cao Jin , Adewunmi Oluwatoyosi , Ferreon Josephine C , Ferreon Allan Chris M , Neilson Joel R , Mancini Michael A , Chen Xi , Kim Jongchan , Ma Li , Li Wenbo , Rosen Jeffrey M
Published: December 2019

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely ‘hijacked’ by cytoplasmic Malat1 to the cytoplasm, resulting in the depletion of nuclear TDP-43 and redistribution of TDP-43 binding to repetitive element transcripts and mRNAs encoding mitotic and nuclear-cytoplasmic regulators. The SINE promotes Malat1 nuclear retention by facilitating Malat1 binding to HNRNPK, a protein that drives RNA nuclear retention, potentially through direct interactions of the SINE with KHDRBS1 and TRA2A, which bind to HNRNPK. Losing these RNA–protein interactions due to the SINE deletion likely creates more available TDP-43 binding sites on Malat1 and subsequent TDP-43 aggregation. These results highlight the significance of lncRNA TEs in TDP-43 proteostasis with potential implications in both cancer and neurodegenerative diseases.
Structural basis for the evolution of cyclic phosphodiesterase activity in the U6 snRNA exoribonuclease Usb1
Authors: Nomura Yuichiro , Montemayor Eric J , Virta Johanna M , Hayes Samuel M , Butcher Samuel E
Published: December 2019

U6 snRNA undergoes post-transcriptional 3′ end modification prior to incorporation into the active site of spliceosomes. The responsible exoribonuclease is Usb1, which removes nucleotides from the 3′ end of U6 and, in humans, leaves a 2′,3′ cyclic phosphate that is recognized by the Lsm2–8 complex. Saccharomycescerevisiae Usb1 has additional 2′,3′ cyclic phosphodiesterase (CPDase) activity, which converts the cyclic phosphate into a 3′ phosphate group. Here we investigate the molecular basis for the evolution of Usb1 CPDase activity. We examine the structure and function of Usb1 from Kluyveromyces marxianus, which shares 25 and 19% sequence identity to the S. cerevisiae and Homo sapiens orthologs of Usb1, respectively. We show that K. marxianus Usb1 enzyme has CPDase activity and determined its structure, free and bound to the substrate analog uridine 5′-monophosphate. We find that the origin of CPDase activity is related to a loop structure that is conserved in yeast and forms a distinct penultimate (n – 1) nucleotide binding site. These data provide structural and mechanistic insight into the evolutionary divergence of Usb1 catalysis.
Blunt and Non-Blunt Cannabis Use and Risk of Subsequent Combustible Tobacco Product Use Among Adolescents
Authors: Mayer Margaret E , Kong Grace , Barrington-Trimis Jessica L , McConnell Rob , Leventhal Adam M , Krishnan-Sarin Suchitra
Published: December 2019

Introduction

Cannabis—including blunts (cannabis rolled in tobacco-containing cigar casing) —is commonly the first substance used among adolescents and may increase the likelihood of subsequent initiation of combustible tobacco products.

Aims and Methods

Data were pooled from two prospective studies of adolescents in California and Connecticut (total N = 4594). Logistic regression models assessed the association of baseline ever blunt use and ever non-blunt cannabis use (vs. never cannabis use) with subsequent initiation of any combustible tobacco-only product (ie, cigarettes, cigars, or cigarillos) by 1-year follow-up after adjustment for demographic characteristics and other tobacco product use at baseline. We also assessed whether estimates differed by prior e-cigarette or hookah use at baseline.

Results

Among never combustible tobacco-only product users (N = 2973), 221 (7.4%) had ever used a blunt and 114 (3.8%) had ever used only non-blunt cannabis at baseline. Blunt use (adjusted odds ratio [AOR] = 1.98, 95% confidence interval [CI]: 1.30 to 3.01) and non-blunt cannabis use (AOR = 2.38, 95% CI: 1.41 to 4.00) were independently associated with greater odds of combustible tobacco-only product initiation by follow-up. Among those who had not tried e-cigarettes or who had not tried hookah, blunt use and non-blunt cannabis use were associated with significantly increased odds of combustible tobacco product initiation; among those who had tried e-cigarettes or hookah, the association was not significant.

Conclusions

We found blunt and non-blunt cannabis use to be associated with subsequent combustible tobacco-only product initiation, particularly among adolescents who had not also tried other products containing nicotine.

Implications

Adolescent-focused tobacco prevention efforts should consider incorporating cannabis products, including blunts. More research is needed to understand how blunt use and cannabis use more broadly are associated with initiation of tobacco products.
The plight of the skyscraper wean: public health and the Jeely Piece Song
Authors: Shaw David M
Published: December 2019

In this Chekhov's Corner article, I explore the public health lessons of a famous Scottish folk song. The Jeely Piece Song uses humour to highlight the health inequalities and other challenges facing children in one of Glasgow's new townships in the 1960s, some of which still persist today.
Factors Affecting Patient Prioritization Decisions at Admission to Home Healthcare
Authors: Topaz Maxim , Naylor Mary D. , Holmes John H. , Bowles Kathryn H.
Published: December 2019

There is a lack of evidence on how to identify high-risk patients admitted to home healthcare. This study aimed (1) to identify which disease characteristics, medications, patient needs, social support characteristics, and other factors are associated with patient priority for the first home health nursing visit; and (2) to construct and validate a predictive model of patient priority for the first home health nursing visit. This was a predictive study of home health visit priority decisions made by 20 nurses for 519 older adults. The study found that nurses were more likely to prioritize patients who had wounds (odds ratio = 1.88), comorbid condition of depression (odds ratio = 1.73), limitation in current toileting status (odds ratio = 2.02), higher number of medications (increase in odds ratio for each medication = 1.04), and comorbid conditions (increase in odds ratio for each condition = 1.04). This study developed one of the first clinical decision support tools for home healthcare called “PREVENT”. (PRiority home health Visit Tool). Further work is needed to increase the specificity and generalizability of the tool and to test its effects on patient outcomes.
Complicated Diverticulitis
Authors: Mendez-Pastor Alvaro , Garcia-Henriquez Norbert
Published: December 2019

CASE SUMMARY:

A 62-year-old previously healthy man presented with left lower quadrant pain and fever. Physical examination showed left lower quadrant peritonitis. Computed tomography scan showed a pelvic abscess with extraluminal air (Fig. 1). Intravenous antibiotics were started, and CT-guided percutaneous drainage was performed. The drain was removed 1 week after discharge. One week later, he presented with dysuria and pneumaturia and was started on antibiotics. Colonoscopy confirmed diverticulosis with no other mucosal abnormalities. He underwent a successful laparoscopic sigmoidectomy with colovesical fistula takedown.
Direct Cost Related to Stroke
Authors: Pucciarelli Gianluca , Rebora Paola , Arisido Maeregu Woldeyes , Ausili Davide , Simeone Silvio , Vellone Ercole , Alvaro Rosaria
Published: December 2019

Background

After discharge from a rehabilitation hospital, stroke survivors and their families may face considerable stroke-related direct costs. The total amount could be ascribed to the costs of formal and informal care and to the equipment or materials needed for care.

Objectives

This study aims to describe the direct costs incurred after a stroke by survivors during their first poststroke year and to analyze the basic predictors of these costs.

Methods

Stroke survivors (N = 415) were enrolled for this study during discharge from rehabilitation hospitals (baseline) and interviewed at 3, 6, 9, and 12 months after discharge for a longitudinal study. The trend of the direct costs incurred during the follow-up (from T1 to T4; n = 239) was evaluated using a linear mixed-effects model. The mixed-effects model was used to identify the baseline predictors of the incurred direct costs from the stroke survivors.

Results

During the first year after discharge, stroke survivors spent approximately $3700 on stroke-related direct (ie, medical and nonmedical) costs. The highest direct costs occurred during the first 6 months, although there was not a significant change over time. The higher direct costs incurred were predicted by the linear effect of time, by the educational level (higher vs low), and by the lower Barthel Index score, whereas a higher perceived cost was predicted only by the linear effect of time and by the lower Barthel Index score.

Conclusion

In the first poststroke year, direct costs have remained stable over time and can be predicted by the level of education and physical functioning. The identification of specific direct cost predictors would be helpful for developing more socially and economically tailored interventions for stroke survivors in their first year after their stroke.
Attitudes to Medication—Treatment Among Patients and Caregivers
Authors: Chauhan Nidhi , Chakrabarti Subho , Grover Sandeep
Published: December 2019

Background

Attitudes toward medication treatment are thought to significantly influence adherence in bipolar disorder (BD) and schizophrenia. However, the actual impact of patients' treatment attitudes on adherence and determinants of attitudes is still uncertain.

Methods

A longitudinal examination of treatment attitudes and their correlates was conducted among patients with BD and their caregivers compared with those with schizophrenia. Structured assessments of symptom severity, functioning, insight, medication side effects, knowledge of illness, medication adherence, treatment attitudes, and treatment satisfaction were performed among 176 selected patients (106 with BD and 70 with schizophrenia) and their caregivers. Participants were reassessed on these parameters at 3 and 6 months.

Results

Rates of nonadherence at baseline varied widely between self-reports, clinician ratings, and serum levels. Though symptoms and functioning improved with treatment, overall rates of nonadherence increased in the first 3 months because of early dropouts and remained stable thereafter. However, treatment attitudes and treatment satisfaction remained largely unchanged among patients and caregivers. Both positive and negative attitudes were commonly held and patients' attitudes did not differ between BD and schizophrenia. Patients' attitudes were significantly associated with adherence, insight, knowledge about illness, treatment satisfaction, symptom severity, social disadvantage, and side effects together with caregivers' knowledge, attitudes, and satisfaction. Caregivers of patients with schizophrenia were more knowledgeable and had more positive attitudes than patients.

Conclusions

Patients' attitudes to medication treatment are associated with adherence over time. They are relatively enduring and mainly associated with insight, knowledge of illness, and treatment satisfaction among patients and their caregivers. These findings could inform psychosocial interventions aiming to improve treatment attitudes and adherence in BD and schizophrenia.
The efficacy of celecoxib for pain management of arthroscopy
Authors: Wan Ruijie , Li Pin , Jiang Heng
Published: December 2019

Background:

The efficacy of celecoxib for pain management of arthroscopy remains controversial. We conduct a systematic review and meta-analysis to assess if celecoxib before the surgery decreases postoperative pain intensity of arthroscopy.

Methods:

We search PubMed, Embase, Web of science, EBSCO, and Cochrane library databases for randomized controlled trials (RCTs) assessing the effect of celecoxib versus placebo on pain control of arthroscopy.

Results:

Five RCTs are included in the meta-analysis. Celecoxib is administered at 200 mg or 400 mg dosage before the surgery. Overall, compared with control group for arthroscopy, preemptive celecoxib has remarkably positive impact on pain scores at 2 to 6 hours (standard mean difference (SMD) = −0.66; 95% confidence interval (CI) = −0.95 to −0.36; P < .0001) and 24 hours after the surgery (SMD = −1.26; 95% CI = −1.83 to −0.70; P < 0.0001), analgesic consumption (SMD  = −2.73; 95% CI = −5.17 to −0.28; P = .03), as well as the decrease in adverse events (risk ratio (RR) = 0.56; 95% CI = 0.39 to 0.79; P = .001), but shows no obvious effect on first time for analgesic requirement (SMD  = 0.02; 95% CI = −0.22 to 0.26; P = .87), nausea, or vomiting (RR = 0.70; 95% CI = 0.42 to 1.17; P = .18).

Conclusion:

Celecoxib administered at 200 mg or 400 mg dosage before the surgery decreases postoperative pain intensity of arthroscopy.
Aspartate aminotransferase to platelet ratio can reduce the need for transient elastography in Chinese patients with chronic hepatitis B
Authors: Yue Wei , Li Yan , Geng Jiawei , Wang Ping , Zhang Li
Published: December 2019

In the absence of liver biopsy and transient elastography (TE), aspartate aminotransferase to platelet ratio (APRI), fibrosis-4 score (FIB-4), and gammaglutamyl transpeptidase to platelet ratio (GPR) are simple and inexpensive methods for the detection of liver fibrosis. Aims: We compared the performance of APRI, FIB-4, and GPR scores against TE in predicting the presence of liver fibrosis and cirrhosis, determined the optimal cut-off values for fibrosis and cirrhosis prediction, and reviewed the need for further TE assessment in resource-limited areas in China. Methods: TE and basic laboratory tests were performed in 2014 consecutive patients with chronic hepatitis B (CHB), and then compared to APRI, FIB-4, and GPR. Results: For the detection of significant fibrosis, the areas under the receiver operating characteristic (AUROC) curves for APRI, FIB-4, and GPR were 0.83, 0.75, and 0.77, respectively. For the detection of cirrhosis, the AUROC curves for APRI, FIB-4, and GPR were 0.90, 0.84, and 0.84, respectively. The cutoff of APRI was 0.35, with 78% sensitivity and 63% negative predictive value (NPV), to exclude significant fibrosis (F ≥ 2). At an APRI of 0.6, results showed a 94% specificity, 100% positive predictive value (PPV) and 7.9 positive likelihood ratio (PLR) in detecting significant fibrosis. Thus, patients with an APRI of <0.35 or >0.6 demonstrated correct prediction of liver fibrosis. These results translated to 1250 out of the 2014 patients avoiding the need for TE with a diagnostic accuracy of >80%. Conclusions: The APRI score accurately assessed fibrosis and reduced the need for TE in almost two-thirds of Chinese patients with CHB.
A case report of acute fibrinous and organizing pneumonia
Authors: Wang Kaige , Du Xinmiao , Wu Qian , Cheng Deyun
Published: December 2019

Rationale:

Acute fibrinous and organizing pneumonia (AFOP) is a newly evolving rare non-infectious lung pathology, characterized by intra-alveolar fibrin balls on histology. It is usually difficult to be diagnosed and mistaken for other lung diseases.

Patient concerns:

In this article, an interesting case about a male patient with a 15-day history of high-grade fever, chills, and no productive cough was presented. He was misdiagnosed as the lung infection early, but exhibited no response to the antibiotic therapy.

Diagnosis:

The diagnosis of AFOP was determined by the lung biopsy and pathology.

Interventions:

With the diagnosis of AFOP, all antibiotics were discontinued, and 40 mg methylprednisolone daily was given intravenously.

Outcomes:

The patient responded well to the treatment with steroids.

Lessons:

AFOP is a rare lung disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of “fibrin balls”. Lung biopsy and histopathology were the most important diagnostic methods for the AFOP. Glucocorticoid was an effective drug for the treatment. Subacute patients of AFOP have excellent prognosis with corticosteroids.
An unusual case report of unilateral parotid gland sarcoidosis with spontaneous remission
Authors: Diamantopoulos Panagiotis T. , Charakopoulos Emmanouil , Viniou Nora-Athina , Diamantopoulou Lydia , Gaggadi Maria
Published: December 2019

Rationale:

Parotid gland sarcoidosis is a well-recognized, but uncommon disease entity. Parotidectomy is most commonly performed to establish the diagnosis and most patients are treated with corticosteroids.

Patient concerns:

A young female patient presented with right parotid enlargement and developed symptoms of facial nerve palsy during diagnostic investigation.

Diagnoses:

A fine-needle aspiration cytology showed granulomatous inflammation. The diagnosis of sarcoidosis was eventually established based on the demonstration of the characteristic lambda and panda signs by a Gallium-67 scintigraphy.

Interventions:

No specific pharmacologic therapy was initiated.

Outcomes:

The patient's symptoms regressed completely over a period of 3 months. Additionally, she remains asymptomatic 2 years later.

Lessons:

This case underlines the importance of not initiating corticosteroids in all patients with parotid gland sarcoidosis and suggests that parotidectomy can be avoided in the presence of characteristic for sarcoidosis imaging findings.
Perioperative outcomes in geriatric patients undergoing hip fracture surgery with different anesthesia techniques
Authors: Chen Dong Xu , Yang Lei , Ding Lin , Li Shi Yue , Qi Ya Na , Li Qian
Published: December 2019

Background:

Previous meta-analyses assessing anesthetic techniques in adult patients undergoing hip fractures surgery are available. However, whether the anesthetic technique is associated with risk of mortality and complications in geriatric patients with hip fractures remains unclear. This study was conducted to assess postoperative outcomes of anesthesia technique in geriatric patients undergoing hip fracture surgery.

Methods:

Cochrane Library, PubMed, EMBASE, MEDLINE, CNKI, and CBM were searched from inception up to May 25, 2018. Observational studies and randomized controlled trials (RCTs) that assessed the perioperative outcomes of technique of anesthesia (general or regional [epidural/spinal/neuraxial]) in geriatric patients (≥60 years old) undergoing hip fracture surgery were included. Two investigators independently screened studies for inclusion and performed data extraction. Heterogeneity was assessed by the I
2 and Chi-square tests. The odds ratio (OR) of the dichotomous data, mean difference (MD) of continuous data, and 95% confidence intervals (CI) were calculated to assess the pooled data.

Results:

Eleven retrospective and 2 RCTs were included. There was no difference in 30-day mortality (OR = 0.96; 95% CI 0.86–1.08; P = .51) between the general and regional anesthesia groups. In-hospital mortality (OR = 1.26; 95% CI 1.17–1.36; P < .001), acute respiratory failure (OR = 2.66; 95% CI 2.34–3.02; P < .001), length of hospital stay (MD = 0.33; 95% CI 0.24–0.42; P < .001), and readmission (OR = 1.09; 95% CI 1.01–1.18; P = .03) were significantly reduced in the regional anesthesia group. Pneumonia (OR = 0.99; 95% CI 0.91–1.07; P = .79), heart failure (OR = 0.97; 95% CI 0.86–1.09; P = .62), acute myocardial infraction (OR = 1.07; 95% CI 0.99–1.16; P = .10), acute renal failure (OR = 1.32; 95% CI 0.97–1.79; P = .07), cerebrovascular accident (OR = 1.08; 95% CI 0.82–1.42; P = .58), postoperative delirium (OR = 1.51; 95% CI 0.16–13.97; P = .72), and deep vein thrombosis/pulmonary embolism (OR = 1.42; 95% CI 0.84–2.38; P = .19) were similar between the two anesthetic techniques.

Conclusion:

General anesthesia is associated with increased risk of in-hospital mortality, acute respiratory failure, longer hospital stays, and higher readmission. There is evidence to suggest that regional anesthesia is associated with improved perioperative outcomes. Large RCTs are needed to explore the most optimal anesthetic techniques for geriatric patients with hip fractures before drawing final conclusions.

PROSPERO registration number:

CRD42018093582.
Compound danshen dripping pills combined with trimetazidine in treating unstable angina pectoris
Authors: Yao Dongfeng , Wang Chuan , Han Lihua , Zhang Pan , Liu Jiping , Wang Bin , Zhang Enhu
Published: December 2019

Background:

Compound danshen dripping pills (CDDP) and trimetazidine (TMZ) are commonly used in the treatment of unstable angina pectoris (UAP). Currently, the combination of CDDP and TMZ has been widely used for UAP. However, the clinical evidence CDDP combined with TMZ for treating UAP is not sufficient.

Methods:

We searched for randomized controlled trials testing CDDP combined with TMZ for the treatment of UAP in Chinese National Knowledge Infrastructure database, VIP database, Chinese Biological and Medicine database, Wangfang database, MEDLINE, EMBASE, Cochrane Library, and Web of Science. Extracted data are analyzed using Review Manager 5.3 software. The quality evaluation, forest plots and funnel plots will be conducted by RevMan5.3 software. Moreover, subgroup analysis and sensitivity analysis will also be completed by RevMan5.3.

Results:

This systematic review will provide powerful clinical evidence of combination CDDP and TMZ for treating UAP.

Conclusions:

This systematic review will be provided up-to-date clinical evidence to evaluate the effectiveness and safety of CDDP combined with TMZ for the treatment of parents with UAP.

Registration Number: PROSPERO CRD42019143100
Correlation between FAS single nucleotide polymorphisms and breast carcinoma susceptibility in Asia
Authors: Chen Ying , Wang Hanfei , Yan Yunwen , Ren Min , Yan Cunye , Wang Benzhong
Published: December 2019

Background:

FAS cell surface death receptor (FAS) gene has 2 common single nucleotide polymorphisms (SNPs) in its promoter, FAS-1377G > A (rs2234767) and FAS-670A > G (rs1800682). Several studies have investigated the role of these 2 polymorphisms in etiology of breast cancer in Asian population while the outcomes are inconsistent. To derive a more precise assessment of the association between breast cancer susceptibility with FAS gene promoter SNPs, a meta-analysis of published studies was performed.

Material and methods:

We systematically searched PubMed, Embase, Web of Science, and the Chinese biomedical database (CBM) for papers published until November 1, 2018. Odds ratio (OR) with 95% confidential interval (95%CI) was conducted to evaluate the associations. Statistical analysis was conducted using Stata13.0 software. A total of 8 studies covering 2564 cases and 2633 controls were included.

Results:

The integrated results suggest the following: For the FAS-1377G/A polymorphism, we only found significant associations for allele G vs allele A (OR = 1.100, 95%CI = 1.004–1.206, P = .040). After stratification by ethnicity, a significant association was observed only for the AA+GA vs GG genotype in East Asian populations (OR = 1.177, 95% CI = 1.010–1.371, P = .037). The association was not found in West Asian populations. For the FAS -670A/G polymorphism, no association with cancer risk was found in any comparison model. Sensitivity analysis suggests that the meta-analysis results obtained after excluding any single study were similar to the original ones, suggesting that the meta-analysis results were not significantly affected by any single study.

Conclusion:

These results indicated that FAS-1377G/A polymorphism may contribute to the increased breast cancer susceptibility and could be a promising target for cancer risk prediction. Further studies are needed to determine if the FAS gene confers a risk of breast cancer in other ethnic groups, such as Africans and Latin Americans.
Spinal rosette-forming glioneuronal tumor
Authors: Hamauchi Shuji , Tanino Mishie , Hida Kazutoshi , Sasamori Toru , Yano Shunsuke , Tanaka Shinya
Published: December 2019

Rationale:

Rosette-forming glioneuronal tumor (RGNT) is a rare tumor which has been first reported as the fourth ventricle tumor by Komori et al and is classified as a distinct clinicopathological entity by the WHO Classification of Tumors of the Central Nervous System as in 2007. Although RGNTs were reported to occur in both supratentorial and inflatentorial sites, only 4 case reports of spinal RGNT have been demonstrated.

Patient concerns:

A 37-year-old female presenting with slowly progressing right-sided clumsiness. Cervical magnetic resonance imaging revealed a spinal intramedullary tumor between the C2 and C5 levels.

Diagnoses:

Pathological analysis showed unique biphasic cellular architecture consisting of perivascular pseudorosettes dominantly with few neurocytic rosettes and diffuse astrocytoma component. The tumor cells composed of perivascular pseudorosettes showed positivity for both synaptophysin and glial markers such as GFAP and Olig2. Therefore, the diagnosis of RGNT was made.

Interventions:

Gross total resection of the tumor was achieved. No adjuvant chemotherapy nor radiotherapy was conducted after operation.

Outcomes:

At 2 years after the operation, no recurrence was observed.

Lessons:

Although RGNT arising from the spinal cord is extremely rare, we need to consider the tumor as a differential diagnosis for intramedullary spinal cord tumors.
Secondary lower limbs lymphedema in patients with Chikungunya fever
Authors: Almeida Catarina Coelho , Lins Esdras Marques , Soares Brandão Simone Cristina , Pinto Flavia Cristina Morone , de Andrade Aguiar José Lamartine , de Lima Filho José Luiz , Rocha Fernanda Appolônio
Published: December 2019

Chikungunya fever (CHIKF) is an arbovirus characterized by acute fever, myalgia and polyarthralgia. Lymphedema in the lower limbs (LL) was observed in several patients during an outbreak of CHIKF in the state of Pernambuco (Brazil) in 2016. No reports on lymphatic vessels disease due to CHIKF have been described. The aim of the study was to follow lymphatic abnormalities in the LL of 16 patients with CHIKF, using lymphoscintigraphy.

An observational, prospective study with patients in the acute phase of CHIKF (confirmed serological diagnosis) with LL edema submitted to clinical evaluation and lymphoscintigraphy at baseline and after 90 days.

Sixteen patients (81% females) participated in this study. All patients presented with lower limb lymphedema, being 15 (94%) bilateral. Of the 31 limbs affected by lymphedema, 24 (77%) presented abnormalities in lymphatic drainage by lymphoscintigraphy. The delay to visualize pelvic lymph nodes was the most frequent lymphoscintigraphic abnormality, observed in 16 (51,6%) LL. Nine (56%) patients were clinically reevaluated after 90 days, and all 18 LL remained with lymphedema. A second lymphoscintigraphy showed persistent abnormalities in 13 (72%) of the 18 LL.

CHIKF can lead to lymphedema, and lymphedema may persist or progress after 3 months of the acute phases of the disease.
Five Year Follow-up of a Randomized Controlled Trial of Laparoscopic Repair of Very Large Hiatus Hernia With Sutures Versus Absorbable Versus Nonabsorbable Mesh
Authors: Watson David I. , Thompson Sarah K. , Devitt Peter G. , Aly Ahmad , Irvine Tanya , Woods Simon D. , Gan Susan , Game Philip A. , Jamieson Glyn G.
Published: December 2019

Objective:

To determine whether absorbable or nonabsorbable mesh repair of large hiatus hernias is followed by less recurrences at late follow-up compared to sutured repair.

Summary of Background Data:

Radiological recurrences have been reported in up to 30% of patients after repair of large hiatus hernias, and mesh repair has been proposed as a solution. Earlier trials have revealed mixed outcomes and early outcomes from a trial reported previously revealed no short-term advantages for mesh repair.

Methods:

Multicentre prospective double-blind randomized controlled trial of 3 methods of hiatus hernia repair; sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome – hernia recurrence assessed by barium meal X-ray and endoscopy at 3–4 years. Secondary outcomes – clinical symptom scores at 2, 3, and 5 years.

Results:

126 patients were enrolled – 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Clinical outcomes were obtained at 5 years in 89.9%, and objective follow-up was obtained in 72.3%. A recurrent hernia (any size) was identified in 39.3% after suture repair, 56.7% – absorbable mesh, and 42.9% – nonabsorbable mesh (P = 0.371). Clinical outcomes were similar at 5 years, except chest pain, diarrhea, and bloat symptoms which were more common after repair with absorbable mesh.

Conclusions:

No advantages were demonstrated for mesh repair at up to 5 years follow-up, and symptom outcomes were worse after repair with absorbable mesh. The longer-term results from this trial do not support mesh repair for large hiatus hernias.
Effects of hospital-acquired pneumonia on long-term recovery and hospital resource utilization following moderate to severe traumatic brain injury
Authors: Kumar Raj G. , Kesinger Matthew R. , Juengst Shannon B. , Brooks Maria M. , Fabio Anthony , Dams-O'Connor Kristen , Pugh Mary Jo , Sperry Jason L. , Wagner Amy K.
Published: December 2019

BACKGROUND

Individuals with traumatic brain injury (TBI) have extended inpatient hospital stays that include prolonged mechanical ventilation, increasing risk for infections, including pneumonia. Studies show the negative short-term effects of hospital-acquired pneumonia (HAP) on hospital-based outcomes; however, little is known of its long-term effects.

METHODS

A prospective cohort study was conducted. National Trauma Databank and Traumatic Brain Injury Model Systems were merged to derive a cohort of 3,717 adults with moderate-to-severe TBI. Exposure data were gathered from the National Trauma Databank, and outcomes were gathered from the Traumatic Brain Injury Model Systems. The primary outcome was the Glasgow Outcome Scale—Extended (GOS-E), which was collected at 1, 2, and 5 years postinjury. The GOS-E was categorized as favorable (>5) or unfavorable (≤5) outcomes. A generalized estimating equation model was fitted estimating the effects of HAP on GOS-E over the first 5 years post-TBI, adjusting for age, race, ventilation status, brain injury severity, injury severity score, thoracic Abbreviated Injury Scale score of 3 or greater, mechanism of injury, intraventricular hemorrhage, and subarachnoid hemorrhage.

RESULTS

Individuals with HAP had a 34% (odds ratio, 1.34; 95% confidence interval, 1.15–1.56) increased odds for unfavorable GOS-E over the first 5 years post-TBI compared with individuals without HAP, after adjustment for covariates. There was a significant interaction between HAP and follow-up, such that the effect of HAP on GOS-E declined over time. Sensitivity analyses that weighted for nonresponse bias and adjusted for differences across trauma facilities did not appreciably change the results. Individuals with HAP spent 10.1 days longer in acute care and 4.8 days longer in inpatient rehabilitation and had less efficient functional improvement during inpatient rehabilitation.

CONCLUSION

Individuals with HAP during acute hospitalization have worse long-term prognosis and greater hospital resource utilization. Preventing HAP may be cost-effective and improve long-term recovery for individuals with TBI. Future studies should compare the effectiveness of different prophylaxis methods to prevent HAP.

LEVEL OF EVIDENCE

Prospective cohort study, level III.
Elioraea thermophila sp. nov., a thermophilic bacterium from hot spring of the class Alphaproteobacteria, emended description of the genus Elioraea and proposal of Elioraeaceae fam. nov.
Authors: Habib Neeli , Khan Inam Ullah , Xiao Min , Hejazi Mohammad Saeid , Tarhriz Vahideh , Zhi Xiao-Yang , Li Wen-Jun
Published: December 2019

A Gram-staining-negative, aerobic, curved rod-shaped and thermophilic bacterial strain, designated YIM 72297T, was isolated from a sediment sample collected from a hot spring in Tengchong county, Yunnan province, south-west China. Growth was observed at pH 5.0–9.0 with an optimum of pH 7.0–7.5, and at 45–60 °C with an optimum of 55 °C. Positive for catalase and oxidase. The 16S rRNA gene sequence comparison indicated that strain YIM 72297T was most closely related to

Elioraea tepidiphila

DSM 17972T (96.9 %) and showed <91 % sequence similarities to members of the order

Rhodospirillales

. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YIM 72297T formed a distinct lineage within the genus

Elioraea

, and revealed that the genus

Elioraea

formed a novel family-level clade in the order

Rhodospirillales

. The ANI and the dDNA-DNA hybridization estimate values between strains YIM 72297T and

Elioraea tepidiphila

DSM 17972T were 70.8 and 20.1 %, respectively. Strain YIM 72297T contained Q-10 as the predominant ubiquinone. The major fatty acids (>5 %) were summed C18 : 0 (35.8 %), summed feature 8 (30.1 %), C16 : 0 (12.6 %), C18 : 1 2OH (5.6 %) and C16 : 0 2OH (5.4 %). The polar lipids consisted of phosphatidylcholine, phosphatidylethanolamine, diphosphosphatidylglycerol and phosphatidylglycerol in addition to two unidentified aminolipids. The DNA G+C content of YIM 72297T was 70.8 mol% (draft genome). On the basis of the polyphasic taxonomic evidence presented in this study, strain YIM 72297T should be classified as representing a novel species of the genus

Elioraea

, for which the name

Elioraea thermophila

sp. nov. is proposed, with the type strain YIM 72297T (=CCTCC AB 2017169T=KCTC 62323T). In addition, a novel family, Elioraeaceae fam. nov., is proposed to accommodate the genus

Elioraea

.
Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry
Authors: Hernando-Pérez Mercedes , Martín-González Natalia , Pérez-Illana Marta , Suomalainen Maarit , Ostapchuk Philomena , Condezo Gabriela. N. , Menéndez M. , Greber Urs F. , Hearing Patrick , Pablo Pedro J. de , Martín Carmen San
Published: December 2019

Adenovirus minor coat protein VI contains a membrane-disrupting peptide which is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and non-infectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wildtype (Ad5-wt) particles. Cryo-EM difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating.

Significance Statement

Correct assembly of an adenovirus infectious particle involves the highly regulated interaction of more than ten different proteins as well as the viral genome. Here we examine the interplay between two of these proteins: the major core protein VII, involved in genome condensation, and the multifunctional minor coat protein VI. Protein VI binds to the inner surface of adenovirus hexons (trimers of the major coat protein) and contains a lytic peptide which must be released during entry to ensure endosome rupture. We present data supporting a dynamic competition model between proteins VI and VII for hexon binding during assembly. This competition facilitates the release of the lytic peptide from the hexon cavity and ensures virus escape from the early endosome.
Highly clustered de novo frameshift variants in the neuronal splicing factor NOVA2 result in a specific abnormal C terminal part and cause a severe form of intellectual disability with autistic features
Authors: Mattioli Francesca , Hayot Gaelle , Drouot Nathalie , Isidor Bertrand , Courraud Jérémie , Mau-Them Frederic Tran , Sellier Chantal , Hinckelmann Maria-Victoria , Goldman Alica , Telegrafi Aida , Boughton Alicia , Gamble Candace , Moutton Sebastien , Quartier Angélique , Jean Nolwenn , Ness Paul Van , Grotto Sarah , Nambot Sophie , Douglas Ganka , Si Yue Cindy , Chelly Jamel , Shad Zohra , Kaplan Elisabeth , Dineen Richard , Golzio Christelle , Charlet Nicolas , Jean-Louis Mandel , Amélie Piton
Published: December 2019

The Neuro-Oncological Ventral Antigen 2 NOVA2 protein is a major factor regulating neuron specific alternative splicing, previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in the NOVA2 gene affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait and abnormal brain MRI. The six variants lead to the same reading frame, adding a common 133 aa long proline rich C-terminus part instead of the last KH RNA binding domain. We detected forty-one genes differentially spliced after NOVA2 inactivation in human neural cells. The mutant NOVA2 protein shows decreased ability to bind a target RNA, to regulate specific splicing events and to rescue the phenotype of altered retinotectal axonal pathfinding induced by loss of NOVA2 ortholog in zebrafish. Our results suggest a partial loss-of-function mechanism rather than a full heterozygous loss of function, although a specific contribution of the novel C terminal extension cannot be excluded on the basis of the genetic findings.
Non-clonal emergence of colistin resistance associated with mutations in the BasRS two-component system in Escherichia coli bloodstream isolates
Authors: Janssen Axel B. , Bartholomew Toby L. , Marciszewska Natalia P. , Bonten Marc J.M. , Willems Rob J.L. , Bengoechea Jose A. , van Schaik Willem
Published: December 2019

Infections by multidrug-resistant Gram-negative bacteria are increasingly common, prompting the renewed interest in the use of colistin. Colistin specifically targets Gram-negative bacteria by interacting with the anionic lipid A moieties of lipopolysaccharides, leading to membrane destabilization and cell death. Here, we aimed to uncover the mechanisms of colistin resistance in nine colistin-resistant Escherichia coli strains and one E. albertii strain. These were the only colistin-resistant strains out of 1140 bloodstream Escherichia isolates collected in a tertiary hospital over a ten-year period (2006 - 2015). Core genome phylogenetic analysis showed that each patient was colonised by a unique strain, suggesting that colistin resistance was acquired independently in each strain. All colistin-resistant strains had lipid A that was modified with phosphoethanolamine. In addition, two E. coli strains had hepta-acylated lipid A species, containing an additional palmitate compared to the canonical hexa-acylated E. coli lipid A. One E. coli strain carried the mobile colistin resistance (mcr) gene mcr-1.1 on an IncX4-type plasmid. Through construction of chromosomal transgene integration mutants, we experimentally determined that mutations in basRS, encoding a two-component signal transduction system, contributed to colistin resistance in four strains. We confirmed these observations by reversing the mutations in basRS to the sequences found in reference strains, resulting in loss of colistin resistance. While the mcr-genes have become a widely studied mechanism of colistin resistance in E. coli, sequence variation in basRS is another, potentially more prevalent but relatively underexplored, cause of colistin resistance in this important nosocomial pathogen.

Importance

Multidrug resistance among Gram-negative bacteria has led to the use of colistin as a last-resort drug. The cationic colistin kills Gram-negative bacteria through electrostatic interaction with the anionic lipid A moiety of lipopolysaccharides. Due to increased use in clinical and agricultural settings, colistin resistance has recently started to emerge. In this study, we used a combination of whole genome sequence analysis and experimental validation to characterise the mechanisms through which E. coli strains from bloodstream infections can develop colistin resistance. We found no evidence of direct transfer of colistin-resistant isolates between patients. The lipid A of all isolates was modified by the addition of phosphoethanolamine. In four isolates, colistin resistance was experimentally verified to be caused by mutations in the basRS genes, encoding a two-component regulatory system. Our data show that chromosomal mutations are an important cause of colistin resistance among clinical E. coli isolates.
Evolution of populations with strategy-dependent time delays
Authors: Miȩkisz Jacek , Bodnar Marek
Published: December 2019

We address the issue of stability of coexistence of two strategies with respect to time delays in evolving populations. It is well known that time delays may cause oscillations. Here we report a novel behavior. We show that a microscopic model of evolutionary games with a unique mixed evolutionarily stable strategy (a globally asymptotically stable interior stationary state in the standard replicator dynamics) and with strategy-dependent time delays leads to a new type of replicator dynamics. It describes the time evolution of fractions of the population playing given strategies and the size of the population. Unlike in all previous models, an interior stationary state of such dynamics depends continuously on time delays and at some point it might disappear, no cycles are present. In particular, this means that an arbitrarily small time delay changes an interior stationary state. Moreover, at certain time delays, there may appear another interior stationary state.

Author summary

Social and biological processes are usually described by ordinary or partial differential equations, or by Markov processes if we take into account stochastic perturbations. However, interactions between individuals, players or molecules, naturally take time. Results of biological interactions between individuals may appear in the future, and in social models, individuals or players may act, that is choose appropriate strategies, on the basis of the information concerning events in the past. It is natural therefore to introduce time delays into evolutionary game models. It was usually observed, and expected, that small time delays do not change the behavior of the system and large time delays may cause oscillations. Here we report a novel behavior. We show that microscopic models of evolutionary games with strategy-dependent time delays, in which payoffs appear some time after interactions of individuals, lead to a new type of replicator dynamics. Unlike in all previous models, interior stationary states of such dynamics depend continuously on time delays. This shows that effects of time delays are much more complex than it was previously thought.
Surfactin production is not essential for pellicle and root-associated biofilm development ofBacillus subtilis
Authors: Thérien Maude , Kiesewalter Heiko T. , Auria Emile , Charron-Lamoureux Vincent , Wibowo Mario , Maróti Gergely , Kovács Ákos T. , Beauregard Pascale B.
Published: December 2019

Secondary metabolites have an important impact on the biocontrol potential of soil-derived microbes. In addition, various microbe-produced chemicals have been suggested to impact the development and phenotypic differentiation of bacteria, including biofilms. The non-ribosomal synthesized lipopeptide ofBacillus subtilis, surfactin, has been described to impact the plant promoting capacity of the bacterium. Here, we investigated the impact of surfactin production on biofilm formation ofB. subtilisusing the laboratory model systems; pellicle formation at the air-medium interface and architecturally complex colony development, in addition to plant root-associated biofilms. We found that the production of surfactin byB. subtilisis not essential for pellicle biofilm formation neither in the well-studied strain, NCIB 3610, nor in the newly isolated environmental strains, but lack of surfactin reduces colony expansion. Further, plant root colonization was comparable both in the presence or absence of surfactin synthesis. Our results suggest that surfactin-related biocontrol and plant promotion inB. subtilisstrains are independent of biofilm formation.