bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross Resistance in S-Methoprene-Resistant Culex quinquefasciatus (Diptera: Culicidae)
Authors: Su Tianyun , Thieme Jennifer , Cummings Robert , Cheng Min-Lee , Brown Michelle Q
Published: September 2020

The juvenile hormone analog S-methoprene is the only synthetic biopesticide that is registered with the United States Environmental Protection Agency to control arthropods of economic importance in public health, livestock, pets, urban, and stored products. The high activity, relative target specificity, and benign environmental profile of S-methoprene have been well documented. While the risk of resistance in mosquitoes to S-methoprene is generally low, there is a lack of information regarding cross resistance in S-methoprene-resistant mosquitoes to other pesticides. In this paper, a population of the southern house mosquito Culex quinquefasciatus Say from southern California acquired low levels of resistance to S-methoprene in the field, where the resistance ratios ranged 7.0- to 8.8-fold as compared with a laboratory reference colony. After 30 generations of laboratory selections by S-methoprene when resistance was elevated to 57.4- to 168.3-fold relative to an unselected population, various levels of cross resistance to other commonly used pesticides were revealed in the selected population. Cross resistance to the microbial mosquito larvicide Lysinibacillus sphaericus (Meyer & Neide) (Bacillales: Bacillaceae) was the most profound, amounting to 77.50- to 220.50-fold. The mechanism and potential management tactics toward cross resistance are discussed to preserve the unique value of this synthetic biopesticide.
Latent Hybridity in Administrative Crisis Management: The German Refugee Crisis of 2015/16
Authors: Eckhard Steffen , Lenz Alexa , Seibel Wolfgang , Roth Florian , Fatke Matthias
Published: September 2020

Studying the so-called refugee crisis in Germany, this article asks about the effectiveness of crisis management by a large number of local administrations, each acting upon the same crisis impulse of a high number of asylum seekers who entered the country in 2015 and 2016. Instead of theorizing the exact administrative design features fit for an effective crisis response, the focus is on the ability of administrations to adjust. We conceptualize such shifts in administrative practices as informal and temporary (latent) deviations from routine action along two dimensions of organizational behavior typically dominant in private and nonprofit sector organizations, respectively: internal flexibility and citizen participation (hybridity). Novel survey data from 235 out of 401 German district authorities are reported. We test the effects of different forms of latent hybridization on administrative effectiveness using regression modeling. Findings indicate that changes in administrative practices towards more flexible and participatory action had a positive impact on self-reported crisis management effectiveness. The effect of flexible action was especially pronounced in districts that were allocated higher shares of asylum seekers. These findings advance theory on crisis management and bottom-up implementation, highlighting the ability of local agencies to shift practices as a key explanatory factor for effective administrative action in exceptional situations.
Obturator hernia: case report
Authors: Mindaye Esubalew Taddese , Giduma Dereje , Tufa Tesfaye H
Published: September 2020

Obturator hernia, protrusion of abdominal content through the obturator foramen, is a rare type of abdominal wall hernia. Late patient presentation is associated with significant morbidity and mortality. We present rare case of obturator hernia causing small bowel obstruction in a 65-year-old-female patient. She presented with crampy abdominal pain, nausea and vomiting of three days duration. She was diagnosed with acute surgical abdomen and managed surgically at Arsi University College of health sciences, Assela, Ethiopia. Intraoperative finding revealed left-side obturator hernia, which is an extremely rare occurrence. Despite delayed presentation, our patient had smooth postoperative recovery. Obturator hernia is exceedingly rare, and it poses a diagnostic challenge as signs and symptoms are often nonspecific, making a preoperative diagnosis difficult. So, it should be considered as differential diagnosis in elderly patients presenting with acute surgical abdomen.
OPEC: Still an ‘Instrument of Change’?
Authors: Gault John , Ait-Laoussine Nordine
Published: September 2020

The Organization of Petroleum Exporting Countries (OPEC) marks its 60th anniversary in 2020. At the time of OPEC’s 20th anniversary in 1980, the organization could celebrate its role as an “instrument of change” that promoted not only members’ interests but also the interests of broad constituencies, including especially developing countries. OPEC and its members had demonstrated how to overcome the negative economic consequences of colonialism, and sought to extend their success to others through the New International Economic Order adopted by the United Nations in 1974. But from the late 1970s onward, the Organization became focused on internal issues of oil market management and, despite its noble expressions and intentions, was unable to bring about the global changes it sought. Today, on OPEC’s 60th anniversary, the central challenge is no longer how to overcome the colonial economic legacy. Instead, the organization has an opportunity to resume its leadership role by adopting policies that defend not only its own members but also broad constituencies—and especially developing countries—against the consequences of global warming. This article suggests how OPEC could rise to the occasion.
Evaluation of Serum GDF15, AFP, and PIVKA-II as Diagnostic Markers for HBV-Associated Hepatocellular Carcinoma
Authors: Chen Juanjuan , Tang Dongling , Xu Chu , Niu Zhili , Li Huan , Li Yan , Zhang Pingan
Published: September 2020

Objective

To evaluate the potential diagnostic value of growth differentiation factor 15 (GDF15) alone and its combination with protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP) for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).

Methods

Serum levels of GDF15, PIVKA-II, and AFP were measured in 110 patients with HBV-associated HCC, 70 patients with HBV-related liver cirrhosis (LC), 70 patients with chronic hepatitis B (CHB), and 110 healthy patients.

Results

Serum GDF15 was positively related to the levels of PIVKA-II and AFP in patients with HCC (r = 0.352 and r = 0.378; all P <.0001). When the receiver operating characteristic (ROC) curve was plotted for patients with HCC vs all control patients, serum GDF15 had diagnostic parameters of an area under the curve (AUC) of 0.693, a sensitivity of 67.30%, and a specificity of 66.70%, which were lower than parameters for PIVKA-II and AFP (all P <.0001). When the ROC curve was plotted for patients with HCC vs patients with LC, the combination of GDF15 and PIVKA-II had the highest diagnostic accuracy of AUC and specificity as compared with other combinations (all P <.0001).

Conclusion

We found that GDF15 is a potent serum marker for the detection of HBV-associated HCC and that PIVKA-II combined with GDF15 can improve diagnostic accuracy for HBV-associated HCC.
Kripke-style Semantics and Completeness for Full Simply Typed Lambda Calculus
Authors: Kašterović Simona , Ghilezan Silvia
Published: September 2020

Full simply typed lambda calculus is the simply typed lambda calculus extended with product types and sum types. We propose a Kripke-style semantics for full simply typed lambda calculus. We then prove soundness and completeness of type assignment in full simply typed lambda calculus with respect to the proposed semantics. The key point in the proof of completeness is the notion of a canonical model.
Dietary patterns and depression risk in older adults: systematic review and meta-analysis
Authors: Wu Pei-Yu , Chen Kuei-Min , Belcastro Frank
Published: September 2020

Context

Diet may be one of the modifiable environmental factors that could reduce depressive symptoms or abate the development of depression without side effects. However, previous reviews mainly focused on general adult populations.

Objective

The aim of this systematic review and meta-analysis was to explore the association between healthy dietary patterns and depression risk in older adults.

Data Sources

Eight databases were searched up to September 2019. The inclusion criteria were older adults aged ≥ 65 years, healthy dietary patterns, depression assessed by a physician or by validated screening tools, and quantitative study design.

Data Extraction

Data were extracted independently by 2 researchers, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed.

Data Analysis

Meta-analysis was conducted by calculating the pooled odds ratio (OR) and 95% CIs. A total of 18 eligible studies were meta-analyzed. Results showed that a healthy dietary pattern is associated with a reduced risk of depression in older adults (OR, 0.85; 95%CI, 0.78–0.92; P < 0.001). There was high heterogeneity (I2 = 64.9%; P < 0.001) among the studies. Subgroup analyses indicated that sample size and depression screening tools were the main sources of study heterogeneity.

Conclusions

An inverse association between healthy dietary patterns and depression risk in older adults was found. However, the high heterogeneity among the studies should be considered.

Systematic Review Registration

PROSPERO registration no. CRD 42020169195.
Analysis of the Function of the Alfalfa Mslea-D34 Gene in Abiotic Stress Responses and Flowering Time
Authors: Lv Aimin , Su Liantai , Wen Wuwu , Fan Nana , Zhou Peng , An Yuan
Published: September 2020

A novel late embryogenesis abundant (LEA) gene, MsLEA-D34, was cloned from alfalfa (Medicago sativa L.). Its function and gene regulatory pathways were studied via overexpression (OE) and RNA interference (RNAi) of the gene in Arabidopsis and in hairy roots of alfalfa, as well as via analyzing key genes related to MsLEA-D34 during developmental phases in alfalfa. The results showed that MsLEA-D34 was a typical intrinsically disordered protein with a high capability for protein protection. Overexpression of MsLEA-D34 increased plant tolerance to osmotic and salt stresses, and caused Arabidopsis early flowering under drought and well-watered conditions. Overexpressing MsLEA-D34 induced up-regulation of FLOWERING LOCUS T (FT) and GIGANTEA (GI) at the flowering phase of Arabidopsis and hairy roots of alfalfa, but only FT was down-regulated in MsLEA-D34-RNAi lines. A positive effect of MsLEA-D34 on FT accumulation was demonstrated in alfalfa hairy roots. An ABA-responsive element (ABRE)-binding transcription factor (MsABF2), a novel transcription factor cloned from alfalfa, directly bound to the RY element in the MsLEA-D34 promoter and activated MsLEA-D34 expression. The above results indicate that MsLEA-D34 can regulate abiotic stress response in plants and influence flowering time of Arabidopsis.
Minimum Wages and Racial Inequality*
Authors: Derenoncourt Ellora , Montialoux Claire
Published: September 2020

The earnings difference between white and black workers fell dramatically in the United States in the late 1960s and early 1970s. This article shows that the expansion of the minimum wage played a critical role in this decline. The 1966 Fair Labor Standards Act extended federal minimum wage coverage to agriculture, restaurants, nursing homes, and other services that were previously uncovered and where nearly a third of black workers were employed. We digitize over 1,000 hourly wage distributions from Bureau of Labor Statistics industry wage reports and use CPS microdata to investigate the effects of this reform on wages, employment, and racial inequality. Using a cross-industry difference-in-differences design, we show that earnings rose sharply for workers in the newly covered industries. The impact was nearly twice as large for black workers as for white workers. Within treated industries, the racial gap adjusted for observables fell from 25 log points prereform to 0 afterward. We can rule out significant disemployment effects for black workers. Using a bunching design, we find no aggregate effect of the reform on employment. The 1967 extension of the minimum wage can explain more than 20% of the reduction in the racial earnings and income gap during the civil rights era. Our findings shed new light on the dynamics of labor market inequality in the United States and suggest that minimum wage policy can play a critical role in reducing racial economic disparities.
Coordinating transnational futurework in fashion design
Authors: Hoppe Alexander D
Published: September 2020

Both quantitative and qualitative research has provided evidence of a fashion system with principled aesthetic transitions. Previous theories of coordination have been proposed at the level of collective behavior, but monopolistic competition at the industry level looms large. Designers and suppliers around the world have the difficult task of anticipating uncertain consumer demand. How are multiple layers of futurework coordinated through global value chains? Drawing on 11 months of ethnographic data from first-tier suppliers in India, I document the role of forecasting in buyer–supplier coordination. I describe the contents of forecasts and show how designers use organizational routines to balance competing requirements for conformity and differentiation. Most importantly, I argue that forecasting information is filtered through calculative spaces and the logic of uncertainty absorption. The consequences of transnational futurework resonate not only through finance and technological innovation, but through aesthetics and embodiment.
Protective effects of honey and bee venom against lipopolysaccharide and carbon tetrachloride-induced hepatoxicity and lipid peroxidation in rats
Authors: Meligi Noha M , Ismail Suzan Alaa , Tawfik Nagy S
Published: September 2020

In the present study, the protective effects of honey and bee venom (BV) either independently or in combination against lipopolysaccharide (LPS) and carbon tetrachloride (CCl4)-induced hepatoxicity, lipid peroxidation, and hematological alterations in male albino rats were investigated. In addition, histopathological alterations of hepatic tissues induced by LPS/CCL4 were recorded. Sixty-four of male albino rats of average weight 120–150 g were included in this study. Rats were divided into eight equal groups of eight. The obtained results demonstrated that treatment with LPS/CCl4 caused an increase in the levels of alpha-fetoprotein, which was accompanied by changes in the hepatic function biomarkers that characterized by the increased levels of transaminases (AST, ALT). The results showed oxidative stress as assigned by the increase in lipid peroxide. Meantime detraction in the antioxidants, including glutathione peroxidase was observed. Interruptions in biochemical parameters accompanied by disturbances in hematological parameters and liver histopathology were resulted due to exposure to LPS/CCl4. This study showed the use of honey and BV provided a protective effect on hepatotoxicity induced by LPS/CCl4. This might have been occurred through the reduction of hepatic transaminases and the “Alpha-fetoprotein” in serum and the equilibration of the antioxidation system, thereby, inhibiting the reactive oxygen species accumulation. Honey and BV administration reestablish disturbed hematological parameters and liver histopathology persuaded by LPS/CCl4. More interesting, we demonstrated that using a combination of the honey and BV showed promising enhancement in their protective effects over the use of just one of the two reagents.
Molecular study of 2019 dengue fever outbreaks in Nepal
Authors: Poudyal Pranita , Sharma Kesari , Dumre Shyam Prakash , Bastola Anup , Chalise Bimal Sharma , Shrestha Bikesh , Poudel Anubhav , Giri Anita , Bhandari Paramanda , Shah Yogendra , Poudel Ram Chandra , Khadka Deegendra , Maharjan Jyoti , Ngwe Tun Mya Myat , Morita Kouchi , Pandey Basu Dev , Pandey Kishor
Published: September 2020

Background

Dengue cases have been continuously reported in Nepal, including some large outbreaks, since its first introduction in 2004. The disease is now expanding towards newer locations above 1400 m high, especially the country's capital city, Kathmandu. In 2019, >14,000 dengue cases including six deaths were reported. This study was aimed at the detection and molecular characterization of dengue virus (DENV) in dengue patients.

Methods

A total of 451 patients were enrolled in this study. Demographic, clinical and laboratory information was collected from dengue patients. Dengue infection was confirmed by antibody/antigen detection assays followed by RT-PCR analysis.

Results

The DENV patients showed fever, body ache, headache, myalgia, retro-orbital pain and arthralgia. The platelets were decreased, serum liver enzymes were increased and leucopenia was seen. Out of 195 patients, 111 (57.0%) were positive for DENV RNA by consensus PCR. We found DENV-2, 70 (63.1%) as the predominant serotype responsible for the 2019 outbreak, while DENV-3 was detected in two patients.

Conclusion

Our findings suggest that DENV-2 was the major serotype causing the 2019 massive outbreak in Nepal. This information will help in disease control programs to understand the molecular epidemiology and its changing trend.
Genetic Variation of Rice Blast (Pyricularia oryzae) Isolates in Laos
Authors: Xangsayasane Phetmanyseng , Boualaphanh Chanthakone , Bounphanousay Chay , Bounphanousay Viengphone , Manivong Phatsalakone , Voradeth Singty , Inthapanya Phoumi , Sato Tadasahi , Obara Mitsuhiro , Hayashi Nagao , Fukuta Yoshimichi
Published: September 2020

The pathogenicity of 192 blast isolates collected from regions across the whole of Laos from 2007 to 2009 showed a wide variation in terms of the frequencies of virulence toward differential varieties (DVs) and the susceptible control cultivar Lijiangxintuanheigu. High frequencies of virulence (>50%) were found in the reactions of DVs for Pit, Pia, Pi3, Pi5(t), Pik-s, Piz-t, Pi19(t), and Pi20(t); intermediate values (from 10 to 50%) were found in DVs for Pib, Pii, Pik-m, Pi1, Pik-h, Pik, Pik-p, Pi7(t), Piz-5, Pita (two lines), Pita-2 (two lines), and Pi12(t); and low frequencies (<10%) were found in DVs for Pish, Piz, and Pi9(t). The blast isolates were classified into three cluster groups: Ia and Ib (low virulence) and II (high virulence), based on the patterns of reaction to them. The blast isolates in cluster group Ia were dominant in rainfed lowland areas, those in Ib were dominant in irrigated lowland areas, and those in II were dominant in upland areas. Cluster groups Ia, Ib, and II were dominant in the Southern, Central, and Northern regions, respectively. Blast races in Laos were distributed according to ecosystems for rice cultivation and geographical regions from south to north with different virulence. These isolates were categorized into 156 races, and the numbers of blast isolates were few in each race. A total of 15 representative isolates were selected from among them as standard differential blast isolates, to develop a differential system.
Localization of the Stem Rust Resistance GenePg2to Linkage Group Mrg20 in Cultivated Oat (Avena sativa)
Authors: Kebede Aida Z. , Bekele Wubishet A. , Mitchell Fetch Jennifer W. , Beattie Aaron D. , Chao Shiaoman , Tinker Nicholas A. , Fetch Thomas G. , McCartney Curt A.
Published: September 2020

Stem rust is an important disease of cultivated oat (Avena sativa) caused by Puccinia graminis f. sp. avenae. In North America, host resistance is the primary strategy to control this disease and is conferred by a relatively small number of resistance genes. Pg2 is a widely deployed stem rust resistance gene that originates from cultivated oat. Oat breeders wish to develop cultivars with multiple Pg genes to slow the breakdown of single gene resistance, and often require DNA markers suited for marker-assisted selection. Our objectives were to (i) construct high density linkage maps for a major oat stem rust resistance gene using three biparental mapping populations, (ii) develop Kompetitive allele-specific PCR (KASP) assays for Pg2-linked single-nucleotide polymorphisms (SNPs), and (iii) test the prediction accuracy of those markers with a diverse panel of spring oat lines and cultivars. Genotyping-by-sequencing SNP markers linked to Pg2 were identified in an AC Morgan/CDC Morrison recombinant inbred line (RIL) population. Pg2-linked SNPs were then analyzed in an AC Morgan/RL815 F2population and an AC Morgan/CDC Dancer RIL population. Linkage analysis identified a common location for Pg2 in all three populations on linkage group Mrg20 of the oat consensus genetic map. The most predictive markers were identified and converted to KASP assays for use in oat breeding programs. When used in combination, the KASP assays for the SNP loci avgbs2_126549.1.46 and avgbs_cluster_23819.1.27 were highly predictive of Pg2 status in panel of 54 oat breeding lines and cultivars.
Beyond Gender Identity Disorder Diagnoses Codes
Authors: Jasuja Guneet K. , de Groot Alexander , Quinn Emily K. , Ameli Omid , Hughto Jaclyn M.W. , Dunbar Michael , Deutsch Madeline , Streed Carl G. , Paasche-Orlow Michael K. , Wolfe Hill L. , Rose Adam J.
Published: September 2020

Background:

Large administrative databases often do not capture gender identity data, limiting researchers’ ability to identify transgender people and complicating the study of this population.

Objective:

The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults.

Research Design:

This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient’s chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code.

Subjects:

Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017.

Results:

We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified.

Conclusion:

In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.
Comparison of Assays for the Diagnosis of Mycoplasma genitalium and Macrolide Resistance Mutations in Self-Collected Vaginal Swabs and Urine
Authors: Chernesky Max , Jang Dan , Martin Irene , Speicher David J. , Clavio Avery , Lidder Ravinder , Ratnam Sam , Smieja Marek , Arias Manuel , Shah Anika
Published: September 2020

Background

The objective was to compare commercial assays on clinical specimens for Mycoplasma genitalium (MG) detection and macrolide resistance mutation (MRM) frequency.

Methods

Three self-collected vaginal swabs (VS) and a first-void urine (FVU) from 300 consented women were tested by Aptima MG (AMG), ResistancePlus MG (RPMG) and Seeplex STD6 ACE (STD6) for detection of MG. Aptima MG and STD6 MG positives were tested for MRM using MG 23S rRNA polymerase chain reaction with Sanger sequencing (23SMGSS) compared with MRM determination in the RPMG assay. Unique AMG positives were tested with confirmatory Aptima assays.

Results

M. genitalium prevalence ranged from 7.1% to 19.7%, influenced by the assay used and the specimen tested. Overall agreements for MG detection were 96.3% (κ = 0.91) for VS and 93.3% (κ = 0.72) for FVU between AMG and RPMG with lower agreements with STD6. Using a rotating reference standard, sensitivities on VS and FVU were 100% and 100% for AMG, 100% and 83.3% for RPMG, and 54.2% and 48.4% for STD6. Specificities were high for RPMG and STD6 and AMG detected extra positives, most of which were confirmed. Macrolide resistance mutation frequency rates testing VS and FVU were 50% (24/48) and 58.1% (18/31) by RPMG compared with 52.5% (31/59) and 23.5% (12/51) by 23SMGSS. MRM overall agreements between RPMG and 23SMGSS were 73.2% (κ = 0.41) for VS and 76.0% (κ = 0.52) for FVU.

Conclusions

Aptima MG detected more cases of MG infections. ResistancePlus MG detection was more effective on VS than on FVU. Seeplex STD6 ACE performance was inferior. The MRM detection component of RPMG agreed with results from 23SMGSS most of the time.
Prospective study of short-term quality-of-life after traumatic rib fractures
Authors: Choi Jeff , Khan Suleman , Hakes Nicholas A. , Carlos Garrison , Seltzer Ryan , Jaramillo Joshua D. , Spain David A.
Published: September 2020

BACKGROUND

Postdischarge convalescence after traumatic rib fractures remains unclear. We hypothesized that patients with rib fractures, even as an isolated injury, have associated poor quality of life (QoL) after discharge.

METHODS

We prospectively enrolled adult patients at our level I trauma center with rib fractures between July 2019 and January 2020. We assessed QoL at 1 and 3 months after discharge using the Trauma-specific Quality-of-Life (T-QoL; 43-question survey evaluating five QoL domains on a 4-point Likert scale, where 4 indicates optimal and 1, worst QoL) and supplementary questionnaires. We used generalized estimating equations to assess T-QoL score trends over time and effect of age, sex, injury pattern, self-perceived injury severity, and Injury Severity Score.

RESULTS

We enrolled 139 patients (108 completed the first and 93 completed both surveys). Three months after discharge, 33% of patients were not working at preinjury capacity, and 7% were still using opioid analgesia. Suffering rib fractures mostly impacted recovery and resilience (T-QoL score, mean [robust standard error] at 1 month, 2.7 [0.1]; 3 months, 3.0[0.1]) and physical well-being domains (1 month, 2.5 [0.1]; 3 months, 2.9[0.1]). Quality of life improved over time across all domains. Compared with patients who perceived their injuries as mild/moderate, patients who perceived their injuries as severe/very severe reported worse T-QoL scores across all domains. In contrast, Injury Severity Score did not affect QoL. Patients 65 years or older (−0.6 [0.1]) and women (−0.6 [0.2]) reported worse functional engagement compared with those 65 years or older and men, respectively.

CONCLUSION

We found that patients with traumatic rib fractures experience suboptimal QoL after discharge. Quality of life improved over time, but even 3 months after discharge, patients reported challenges performing activities of daily living, slower-than-expected recovery, and not returning to work at preinjury capacity. Perception of injury severity had a large effect on QoL. Patients with rib fractures may benefit from close short-term follow-up.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level III.
The management of occult hemothorax in adults with thoracic trauma: A systematic review and meta-analysis
Authors: Gilbert Richard W. , Fontebasso Adam M. , Park Lily , Tran Alexandre , Lampron Jacinthe
Published: September 2020

BACKGROUND

Hemothorax is a common sequelae following thoracic trauma and is associated with significant morbidity and mortality. Current guidelines recommend all traumatic hemothoraces be considered for drainage with tube thoracostomy (TT), regardless of size. With increasing use of computed tomography, smaller hemothoraces not seen on x-ray (defined as an occult hemothorax) are frequently detected.

METHODS

This systematic review was performed to gather data on patients with occult hemothorax managed with TT or without TT (termed expectant management [EM]). MEDLINE, EMBASE, and Cochrane databases from inception to October 2019 were searched for relevant articles. The primary outcome was rates of failure of expectant (conservative) management. Secondary outcomes of interest included predictors of TT insertion, predictors of failure of EM, and morbidity and mortality in patients with occult hemothorax.

RESULTS

We screened 1,329 abstracts from which 6 articles reporting 1,405 patients with occult hemothorax were included. Of these patients, 601 (43.68%) were managed initially with TT, and 802 (56.32%) were managed expectantly. Of the 802 patients managed expectantly, 212 failed conservative management and underwent TT insertion (23.1% pooled failure rate estimate [95% confidence interval, 17.1–29.1%]). The presence of concomitant pneumothorax predicted upfront TT insertion. Of the patients who failed EM, the need for mechanical ventilation and the presence of a large hemothorax predicted failure. Mortality was similar in both groups.

CONCLUSIONS

Conservative treatment of occult hemothorax fails in 23.1% of patients. The presence of hemothorax greater than 300 mL and the need for mechanical ventilation predicted failure of conservative treatment and the need for TT. There was no difference in mortality between EM and TT cohorts. These data suggest that it may be possible to safely observe patients with occult hemothoraces less than 300 mL (1.5 cm pleural stripe) secondary to blunt trauma without upfront TT insertion.

LEVEL OF EVIDENCE

Systematic review and meta-analysis, level III.
Plasmin thrombelastography rapidly identifies trauma patients at risk for massive transfusion, mortality, and hyperfibrinolysis: A diagnostic tool to resolve an international debate on tranexamic acid?
Authors: Barrett Christopher D. , Moore Hunter B. , Vigneshwar Navin , Dhara Sanjeev , Chandler James , Chapman Michael P. , Sauaia Angela , Moore Ernest E. , Yaffe Michael B.
Published: September 2020

BACKGROUND

Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis.

METHODS

Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ2 and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%).

RESULTS

Plasmin TEG provided results faster than all other assays (4.7 ± 2.5–9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1–58.1 minutes; p < 0.001). Plasmin TEG–positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708).

CONCLUSION

Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy.

LEVEL OF EVIDENCE

Diagnostic test, level V.
NLRP3 inflammasome inhibition rescues Hutchinson-Gilford Progeria cellular phenotype and extend longevity of an animal model
Authors: Alcocer-Gómez Elísabet , Castejón-Vega Beatriz , Nuñez-Vasco Jéssica , Lendines-Cordero Débora , Navarro-Pando José M. , Cordero Mario D.
Published: September 2020

Inflammation is a hallmark of aging and accelerated aging syndromes. In this context, inflammation has been associated to the pathophysiology of Hutchinson–Gilford progeria syndrome (HGPS). In this study, we report that progeroid skin fibroblasts and animal models present an hyperactivation of the NLRP3-inflammasome complex. High expression of NLRP3 and caspase 1 was also observed in skin fibroblasts from HGPS associated to the nuclei morphology. Lymphoblast from HGPS also showed increased basal levels of NLRP3 and caspase 1 independent to the induction from metabolic factors. Consistent with these results, Zmpste24−/−showed high expression of Nlrp3 and caspase 1 in heart, liver and kidney and reduced levels of Nlrc3, however these changes were not observed in other inflammasomes. We also show that pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved cellular phenotype, significantly extends the lifespan of these progeroid animals and reduced inflammasome-dependent inflammation. These findings suggest the NLRP3-inflammasome comples as a therapeutic approach for patients with HGPS.
Free-living marine nematodes diversity at Ponta Delgada-São Miguel (Azores archipelago, North-East Atlantic Ocean): first results from shallow soft-bottom habitats
Authors: de Jesús Navarrete Alberto , Aramayo Víctor , Davidson Anitha Mary , Costa Ana Cristina
Published: September 2020

Contrasting (sand, algae, rocky-dominated, mixed) benthic habitats were sampled to characterize marine nematode diversity inhabiting surface sediments in São Miguel (Azores, North-East Atlantic Ocean) in July 2019. Nematodes were extracted from the surface layer of sediments and morphologically identified using light microscopy. Nematode taxonomy was based on living/fresh specimens) to ensure a suitable recognition of morphological traits. Our results provide a preliminary checklist of free-living marine nematode genera from 21 intertidal and sublittoral sandy beach sites along the coast of São Miguel island, Azores archipelago, Portugal. The nematode fauna was represented by 4 orders, 21 families, and 43 genera.Cyatholaimus,DesmodoraandDaptonemahad two morphospecies each. Enoplida was represented by 8 families and 13 genera, while Chromadorida by 7 families and 18 genera, the latter corresponding to the most diverse nematode group. Monhysterida had 5 families and 10 genera and Araeolaimida was represented by a single 1 family and 2 genera. The most common genera (i.e., accounting for 75% of all organisms) includedAdoncholaimus(most abundant genus, 32 specimens),Axonolaimus(18),Cyatholaimus(17),Enoploides(13),Rhabdocoma, andAcanthopharynx(11).ViscosiaandEnoplolaimuswere represented by 7 specimens, whilstHalalaimus,Desmoscolex,Monophostia,Daptonema, andTheristusobtained only 6 each. The dominant nematode taxa of São Miguel island have been commonly previously reported in other coastal habitats including sandy beaches. They can be considered typical meiofaunal components of intertidal sandy beaches. Many of the nematode morphotypes found in São Miguel island could represent new species to science. As far as we know, this is the first report on free-living nematodes for São Miguel Island and for marine shallow water in the Azores. Our findings will serve as an import baseline for future research aiming to improve our understating of nematode communities in volcanic islands such as São Miguel in the Azores archipelago.
Nanobody-mediated control of gene expression and epigenetic memory
Authors: Van Mike V. , Fujimori Taihei , Bintu Lacramioara
Published: September 2020

Targeting chromatin regulators to specific genomic locations for gene control is emerging as a powerful method in basic research and synthetic biology. However, many chromatin regulators are large, making them difficult to deliver and combine in mammalian cells. Here, we developed a new strategy for gene control using small nanobodies that bind and recruit endogenous chromatin regulators to a gene. We show that an antiGFP nanobody can be used to simultaneously visualize GFP-tagged chromatin regulators and control gene expression, and that nanobodies against HP1 and DNMT1 can silence a reporter gene. Moreover, combining nanobodies together or with other regulators, such as DNMT3A or KRAB, can enhance silencing speed and epigenetic memory. Finally, we use the slow silencing speed and high memory of antiDNMT1 to build a signal duration timer and recorder. These results set the basis for using nanobodies against chromatin regulators for controlling gene expression and epigenetic memory.
Asthma-associated variants induceIL33differential expression through a novel regulatory region
Authors: Aneas Ivy , Decker Donna C. , Howard Chanie L. , Sobreira Débora R. , Sakabe Noboru J. , Blaine Kelly M. , Stein Michelle M. , Hrusch Cara L. , Montefiori Lindsey E. , Tena Juan , Magnaye Kevin M. , Clay Selene M. , Gern James E. , Jackson Daniel J. , Altman Matthew C. , Naureckas Edward T. , Hogarth Douglas K. , White Steven R. , Gomez-Skarmeta Jose Luis , Schoetler Nathan , Ober Carole , Sperling Anne I. , Nobrega Marcelo A.
Published: September 2020

Genome-wide association studies (GWAS) have implicated theIL33locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as a strong regulatory elementin vivoandin vitro.Chromatin conformation capture showed that this 5 kb region loops to theIL33promoter, potentially regulating its expression. Supporting this notion, we show that genotype at an asthma-associated SNP, rs1888909, located within the 5 kb region, is associated withIL33gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at theIL33locus mediate allele-specific regulatory activity andIL33expression, providing a novel mechanism through which a regulatory SNP contributes to genetic risk of asthma.
“Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes”
Authors: Gomes Fabio M. , Tyner Miles D.W. , Barletta Ana Beatriz F. , Yenkoidiok-Douti Lampougin , Canepa Gaspar E. , Molina-Cruz Alvaro , Barillas-Mury Carolina
Published: September 2020

Immune priming inAnopheles gambiaemosquitoes following infection withPlasmodiumparasites is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4bound to Evokin, a lipid carrier. HDF increases the proportion of circulating granulocytes and enhances mosquito cellular immunity. We found that Evokin is constitutively produced by hemocytes and fat-body cells, but expression increases in response to infection. Insects synthesize lipoxins, but lack lipoxygenases. Here, we show that the Double Peroxidase (DBLOX) enzyme, present in insects but not in vertebrates, is essential for HDF synthesis. DBLOX is highly expressed in oenocytes in the fat body tissue, and these cells proliferate in response toPlasmodiumchallenge. We provide direct evidence that modifications mediated by the histone acetyltransferase AgTip60 (AGAP01539) are essential for sustained oenocyte proliferation, HDF synthesis and immune priming. We propose that oenocytes function as a population of “memory” cells that continuously release lipoxin to orchestrate and maintain a broad, systemic and long-lasting state of enhanced immune surveillance.
Supraphysiological testosterone induces ferroptosis and activates NF-kappaB mediated immune pathways in prostate cancer through nucleophagy
Authors: Mendonca Janet , Kumar Rajendra , Owoyemi Olutosin , Boyapati Kavya , Thomas Naiju , Kanacharoen Suthicha , Coffey Max , Topiwala Deven , Gomes Carolina , Ozbek Busra , Jones Tracy , Rosen Marc , Dong Liang , Wiens Sadie , Brennen W. Nathaniel , Isaacs John , De Marzo Angelo M. , Markowski Mark , Antonarakis Emmanuel S. , Qian David , Pienta Kenneth , Pardoll Drew , Carducci Michael , Denmeade Samuel , Kachhap Sushant
Published: September 2020

The discovery that androgens play an important role in the progression of prostate cancer (PCa) has led to the development of androgen deprivation therapy as a first line of treatment against PCa. However, paradoxical growth inhibition has been observed, both experimentally and clinically, in a subset of PCa upon administration of supraphysiological levels of testosterone (SupraT). Here we report that SupraT activates cytoplasmic nucleic acid sensors and induces growth inhibition of SupraT-sensitive PCa cells. This is initiated by induction of two parallel autophagy-mediated processes, namely, ferritinophagy and nucleophagy. Consequently, autophagosomal DNA activates nucleic acid sensors that converge on NF-kappaB to drive immune signaling pathways. Chemokines and cytokines secreted by the tumor cells in response to SupraT results in increased migration of cytotoxic immune cells to tumor beds of animal xenografts and patient tumors. Collectively, our findings indicate that SupraT may inhibit a subset of PCa by activating nucleic acid sensors and downstream immune signaling.
Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles
Authors: Lu Maolin , Uchil Pradeep D. , Li Wenwei , Zheng Desheng , Terry Daniel S. , Gorman Jason , Shi Wei , Zhang Baoshan , Zhou Tongqing , Ding Shilei , Gasser Romain , Prévost Jérémie , Beaudoin-Bussières Guillaume , Anand Sai Priya , Laumaea Annemarie , Grover Jonathan R. , Liu Lihong , Ho David D. , Mascola John R. , Finzi Andrés , Kwong Peter D. , Blanchard Scott C. , Mothes Walther
Published: September 2020

SARS-CoV-2 spike (S) mediates entry into cells and is critical for vaccine development against COVID-19. Structural studies have revealed distinct conformations of S, but real-time information that connects these structures, is lacking. Here we apply single-molecule Förster Resonance Energy Transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to hACE2, S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences of convalescent plasma and antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to RBD or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design.
Transient cell-in-cell formation underlies tumor resistance to immunotherapy
Authors: Gutwillig Amit , Santana-Magal Nadine , Farhat-Younis Leen , Rasoulouniriana Diana , Madi Asaf , Luxenburg Chen , Cohen Jonathan , Padmanabhan Krishnanand , Shomron Noam , Shapira Guy , Feinmesser Meora , Zlotnik Oran , Debets Reno , Reticker-Flynn Nathan E. , Rider Peleg , Carmi Yaron
Published: September 2020

Despite the remarkable success of immunotherapy in cancer, most patients will develop resistant tumors. While the main conceptual paradigm suggests that relapsed clones emerge through a process of clonal selection and immunoediting, currently little evidence directly demonstrates this process in epithelial cancers.

To study this process, we established several mouse models in which tumors drastically regress following immunotherapy, yet resistant tumors relapse within a few weeks of treatment cessation. Whole exome analyses indicated that relapsed tumors share hundreds of neo-antigens with the primary tumors and are comparably killed by reactive T cells. Examination of tumor cells that survive immunotherapies revealed that they structure a transient cell-in-cell formation, which is impenetrable to immune-derived cytotoxic compounds and to chemotherapies. This formation is mediated predominantly by a cell-membrane protein on activated T cells, which subsequently induces epidermal growth factor receptors and STAT3 phosphorylation in tumors cells. In contrast to previous reports on cell-in-cell formations, here both cells remain alive and can disseminate into single tumor cells once T cells are no longer present.

Overall, this work highlights a powerful resistance mechanism which enable tumor cells to survive immune pressure and provides a new theoretical framework for combining chemotherapies and immunotherapies.
Susceptibility of domestic swine to experimental infection with SARS-CoV-2
Authors: Pickering Brad S. , Smith Greg , Pinette Mathieu M. , Embury-Hyatt Carissa , Moffat Estella , Marszal Peter , Lewis Charles E.
Published: September 2020

SARS-CoV-2, the agent responsible for COVID-19 has been shown to infect a number of species. The role of domestic livestock and the risk associated for humans in close contact remains unknown for many production animals. Determination of the susceptibility of pigs to SARS-CoV-2 is critical towards a One Health approach to manage the potential risk of zoonotic transmission. Here, pigs undergoing experimental inoculation are susceptible to SARS-CoV-2 at low levels. Viral RNA was detected in group oral fluids and nasal wash from at least two animals while live virus was isolated from a pig. Further, antibodies could be detected in two animals at 11 and 13 days post infection, while oral fluid samples at 6 days post inoculation indicated the presence of secreted antibodies. These data highlight the need for additional livestock assessment to better determine the potential role domestic animals may contribute towards the SARS-CoV-2 pandemic.