bluuebunny/crossref_metadata_2025 huggingface dataset:
Exportation of Monkeypox Virus From the African Continent
Authors: Mauldin Matthew R , McCollum Andrea M , Nakazawa Yoshinori J , Mandra Anna , Whitehouse Erin R , Davidson Whitni , Zhao Hui , Gao Jinxin , Li Yu , Doty Jeffrey , Yinka-Ogunleye Adesola , Akinpelu Afolabi , Aruna Olusola , Naidoo Dhamari , Lewandowski Kuiama , Afrough Babak , Graham Victoria , Aarons Emma , Hewson Roger , Vipond Richard , Dunning Jake , Chand Meera , Brown Colin , Cohen-Gihon Inbar , Erez Noam , Shifman Ohad , Israeli Ofir , Sharon Melamed , Schwartz Eli , Beth-Din Adi , Zvi Anat , Mak Tze Minn , Ng Yi Kai , Cui Lin , Lin Raymond T P , Olson Victoria A , Brooks Tim , Paran Nir , Ihekweazu Chikwe , Reynolds Mary G
Published: August 2020

Background

The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa.

Methods

Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak.

Results

Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers.

Conclusions

Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.
Quantification of Major Metabolites of AB-FUBINACA in Solid Tissues Obtained from an Abuser
Authors: Minakata Kayoko , Hasegawa Koutaro , Nozawa Hideki , Yamagishi Itaru , Suzuki Masako , Kitamoto Takuya , Suzuki Osamu , Watanabe Kanako
Published: August 2020

AB-FUBINACA M3 was reported to be a major metabolite of the drug, but its in vivo concentration in authentic human solid tissues has not been quantified yet. Another metabolite AB-FUBINACA M4 did not receive much attention previously and also has not been quantified yet in any authentic human specimens. The aims of this study are to establish a sensitive method for quantification of M3 and M4 in solid tissues and to compare the metabolite profile of AB-FUBINACA in authentic human specimens in vivo with that produced by human hepatocytes in vitro. The quantification was performed by liquid chromatography (LC)–quadrupole-ion trap-tandem mass spectrometry (MS-MS), and the characterization by LC–quadrupole Orbitrap MS-MS The limits of quantification of M3 were 10 pg/mL and 60 pg/g, and those of M4 were 100 pg/mL and 600 pg/g in urine and tissues, respectively. In the present work, M3 and M4 were identified and quantified in human lung, liver and kidney obtained from a cadaver for the first time; the concentrations of M3 were 226, 255, 202 and 155 pg/mL or g, and those of M4 14,400, 768, 637 and 1,390 pg/mL or g in urine, lung, liver and kidney, respectively. The peak intensity profiles of seven metabolites in these specimens were compared with that produced by human hepatocytes; the top three metabolites in urine specimen were completely different from those of hepatocytes. M3 was reported as the predominant metabolite in several previous works and M4 was listed as a minor metabolite in only one work, but, in this work, M4 has been found to be the major metabolite in all of the authentic urine, lung, liver and kidney specimens. The M3 plus M4 metabolites in lung or kidney were found most recommendable to prove AB-FUBINACA consumption, when urine specimen is lacking.
Robustness of Parametric and Nonparametric Fitting Procedures of Tree-Stem Taper with Alternative Definitions for Validation Data
Authors: Yang Sheng-I , Burkhart Harold E
Published: August 2020

This study aims to evaluate the robustness of parametric and nonparametric procedures using alternative definitions of validation data for loblolly pine. Specifically, four data division strategies were implemented: random selection of one-third of the trees in the data set, selection of the smallest one-third of the trees by diameter at breast height (DBH), selection of the middle third of the trees by DBH, and selection of the largest third of the trees by DBH. Results indicate that tree taper was predicted reasonably well by both procedures when the smallest, medium-sized, or randomly selected trees were withheld for validation. However, when the largest trees were withheld for validation, diameters predicted by the nonparametric random forest algorithm were considerably less accurate than those predicted by the parametric models, especially for diameters near the tree top. When extrapolation is anticipated, a carefully designed data-partitioning strategy should provide some protection against poor results for given prediction objectives.

Study Implications

Parametric tree-stem taper models have been widely applied in forestry. Recently, nonparametric methods with computationally intensive algorithms were proposed for estimating tree taper, but reliability of the methods has not been explicitly examined. In practice, models are commonly applied to predict unknown populations, which may vary from the observations used in model development. This study provides insights for natural resource and forest managers to select appropriate validation procedures when developing models for predicting tree-stem taper and examining robustness of parametric and nonparametric fitting of tree-stem taper under varying levels of interpolation/extrapolation from fitting to validation of data.
Business People in War Times, the ‘Fluid Capital’ and the ‘Shy Diaspora’: The Case of Syrians in Turkey
Authors: AkÇalI Emel , GörmüŞ Evrim
Published: August 2020

Due to intensive conflict, a significant amount of Syrian capital flight has funnelled to Turkey since 2011. Drawing upon fieldwork conducted in five major Turkish cities which have hosted the highest number of Syrian business people, this paper first reveals the convergence of the interests of the host state and of the displaced capital owners, as well as the increasing transnationalization of Syrian economic practices. It then assesses the capacity and/or willingness of the Syrian business people to organize themselves as an interest group regarding their interests in Turkey and to assist the process of conflict resolution in Syria. Finally, the paper reflects upon whether a hybrid identity is in the making within the Syrian business diaspora in Turkey. Our findings suggest that the Syrian business diaspora in Turkey is evolving itself into a transnational business community, and developing hybrid socio-economic practices. Yet, we delineate this flourishing community as ‘shy’ because the issues concerning both domestic and Syrian politics are carefully being avoided to keep stability and unity within. This consequently hinders the Syrian business community to form itself as an interest group in Turkey focused on conflict resolution and post-conflict reconstruction in Syria.
Extra-thoracal migration of the Nuss Bar in corrective surgery for pectus excavatum: a very rare late complication
Authors: Simon Natalie , Kolvekar Shyam , Khosravi Amir
Published: August 2020

Pectus excavatum is a chest wall deformity with an incidence of around 1 in 400 live births. The Nuss procedure is a surgical intervention that aims to restore functional integrity in these patients. We report the first case of bar migration into the stomach necessitating further surgical intervention for removal. Our case presents a rare complication of pectus excavatum repair and highlights the importance of vigilant follow-up in these patients. If bar migration does occur, imaging in the form of X-ray and CT scans may be of use in early detection in order to expedite management.
The League of Nations, autonomy and collective security
Authors: White Nigel D
Published: August 2020

This article tests the assumption that in institutional and legal design the League of Nations was incapable of providing collective security. The lens through which this issue is scrutinised is the concept of institutional legal autonomy, in other words the legal separation of the organisation from its member states. The thinking is not necessarily that the greater the autonomy the greater the potential of the organisation to fulfil its functions, but that the organisation already had sufficient autonomy in international relations to provide an effective form of ‘collective security’, a term that was not found in the Covenant but, by 1935, was being used to describe the response of the League to the Italian invasion of Abyssinia in 1935. This article tests the assumption that the League did not have sufficient autonomy in terms of collective judgment and power to deliver collective security.
Predictors of early, recurrent, and intractable seizures in low-grade glioma
Authors: Jo Jasmin , Nevel Kathryn , Sutyla Ryan , Smolkin Mark , Lopes M Beatriz , Schiff David
Published: August 2020

Background

Seizures are common among patients with low-grade glioma (LGG) and can significantly affect morbidity. We sought to determine the association between the clinical and molecular factors with seizure incidence and refractoriness in LGG patients.

Methods

We conducted a retrospective review at the University of Virginia in patients with LGG (World Health Organization, WHO Grade II) evaluated between 2002 and 2015. Descriptive statistics were calculated for variables of interest, and the Kaplan-Meier method was used to estimate survival curves, which were compared with the log-rank test.

Results

A total of 291 patients were included; 254 had molecular testing performed for presence of an isocitrate dehydrogenase (IDH) mutation and/or 1p/19q codeletion. Sixty-eight percent of patients developed seizures prior to LGG diagnosis; 41% of all patients had intractable seizures. Using WHO 2016 integrated classification, there was no significant difference in seizure frequency during preoperative and postoperative periods or in developing intractable seizures, though a trend toward increased preoperative seizure incidence among patients with the IDH mutation was identified (P = .09). Male sex was significantly associated with higher seizure incidence during preoperative (P < .001) and postoperative periods (P < .001); men were also more likely to develop intractable seizures (P = .01).

Conclusions

Seizures are common among patients with LGG. Differences in preoperative or postoperative and intractable seizure rates by WHO 2016 classification were not detected. Our data showed a trend toward higher seizure incidence preoperatively in patients with IDH-mutant LGG. We describe a unique association between male sex and seizure incidence and intractability that warrants further study.
Behavioral Activation and Inhibition Systems: Further Evaluation of a BIS-BAS Model of Chronic Pain
Authors: Sánchez-Rodríguez Elisabet , Racine Mélanie , Castarlenas Elena , Tomé-Pires Catarina , Galán Santiago , Jensen Mark P , Miró Jordi
Published: August 2020

Objectives

The role of the behavioral inhibition system (BIS) and behavioral activation system (BAS) in function has been evaluated in a wide range of populations. However, research on the role of the BIS and BAS in pain is in its early stages. This study sought to evaluate the utility of a BIS-BAS model of chronic pain.

Methods

Participants were 164 individuals with chronic pain who responded to an online survey. Participants provided information about pain location, intensity, and frequency and completed questionnaires assessing behavioral inhibition and activation sensitivity, pain catastrophizing, pain interference, activity engagement, pain willingness, hope, and pain self-efficacy. Seven hierarchical regression analyses were conducted to test hypothesized associations between BIS and BAS sensitivity and measures of participant function.

Results

BIS scores were significantly and positively associated with pain catastrophizing, anxiety, depression, and pain interference and were negatively associated with activity engagement, hope, and pain self-efficacy (P<0.01). BAS scores showed significant and positive associations with activity engagement and hope and showed significant negative associations with pain catastrophizing and anxiety (P<0.05). Furthermore, BIS sensitivity evidenced stronger associations with all the other study measures than did BAS sensitivity.

Conclusions

The findings provide important new information regarding the utility of the BIS-BAS model of chronic pain. Our results support the idea that BIS activation is more important than BAS activation in explaining a variety of pain-related outcomes, including positive and negative responses to pain, and suggest that modification of the model may be indicated. These results have several theoretical and clinical implications.
Invention disclosures and the slowdown of scientific knowledge
Authors: Link Albert N , Scott John T
Published: August 2020

Invention disclosures are one measure of new scientific knowledge that represents and predicts the future scientific research output of a US federal laboratory. In this article, we document a negative shift in the production function for new scientific knowledge as measured by invention disclosures at one federal laboratory, the National Institute of Standards and Technology, over the first 16 years of the new millennium. We find a negative shift of the production function for new scientific knowledge, and that shift might reflect the coincidence of the information and communication technology revolution that enabled fast science, and the evaluation of research with uncritical use of citation counts that created incentives to focus on incremental research in crowded research topics.
Influence of stocking rate and advancing season on forage intake, digestibility, and ruminal fermentation in steers supplemented with dried distillers grains with solubles while grazing northern Great Plains rangelands1
Authors: Chilcoat Kayla E , Crouse Matthew S , Undi Michael R , Caton Joel S , Neville Bryan W
Published: August 2020

The objectives of this study were to evaluate the effects of stocking rate and advancing season on diet chemical composition, intake, digestibility, and ruminal fermentation in steers supplemented with distillers grains with solubles [0.3% of body weight (BW)] while grazing northern Great Plains rangelands. Angus cross beef steers (n = 188; 320 ± 30.3 kg initial BW) were used to establish targeted stocking rates, and 12 ruminal cannulated steers (272 ± 20.0 kg initial BW) were used for diet sampling while cograzing with the noncannulated animals on 12 pastures (n = 3 per treatment). Stocking rates were set to target 65%, 50%, 35%, and 20% of an average annual above-ground biomass remaining at the end of the grazing season (May–September). Five 10-d collection periods were conducted for May 13–22, June 10–19, July 8–17, August 5–14, and September 2–11. There was no difference in steer BWs or average daily gain during any of the collection periods or between stocking rate (P ≥ 0.10). Organic matter (OM), neutral detergent fiber, and acid detergent fiber of forage masticate samples were not affected (P ≥ 0.25) by stocking rate. Crude protein, and all N fractions of forage masticates also did not differ between stocking rate treatments (P ≥ 0.18). Forage OM intake (grams per kilogram of BW) increased cubically across the entire grazing season (P = 0.05). Organic matter digestibility decreased quadratically (P < 0.01) from May to September. Neutral detergent fiber digestibility showed a cubic effect (P < 0.01) across the grazing season, increasing from May to June, then decreasing till September. Crude protein digestibility decreased linearly (P < 0.01) as the season advanced. Ruminal ammonia and volatile fatty acid (VFA) concentrations were affected by stocking rate × period interactions (P ≤ 0.02). Ruminal pH, ammonia, and VFA concentrations were not affected by the stocking rate (P > 0.13) but were impacted by the advancing season (P < 0.01). Ruminal pH increased quadratically (P ≤ 0.01) with advancing season (6.3 to 6.6 ± 0.05 from May to September, respectively). The results of this study demonstrate that intake, fermentation, and digestibility of northern Great Plains forages were influenced more by seasonal factors associated with forage maturity than stocking rate under the conditions of this study.
Postoperative Syrinx Shrinkage in Spinal Ependymoma of WHO Grade II
Authors: Kobayashi Kazuyoshi , Ando Kei , Machino Masaaki , Tanaka Satoshi , Morozumi Masayoshi , Kanbara Shunsuke , Ito Sadayuki , Inoue Taro , Matsuyama Yukihiro , Ishiguro Naoki , Imagama Shiro
Published: August 2020

Study Design:

A retrospective study of preoperative and postoperative magnetic resonance imaging (MRI) findings in spinal ependymoma.

Objective:

The goal of the study was to examine MRI features, including the syrinx component volume, after surgical resection of spinal ependymoma, and to relate these features to extent of resection and improvement of postoperative neurological status.

Summary of Background Data:

Spinal ependymomas have a variety of MRI findings preoperatively, including a hemorrhage cap sign, gadolinium enhancement, and a spinal tumor cyst. However, little is known about these features on postoperative MRI after tumor resection.

Materials and Methods:

The subjects were 38 patients treated for spinal cord ependymoma of World Health Organization grade II at our hospital. All had a spinal tumor cyst on preoperative MRI. All cases were followed with MRI for >1 year after surgery, including imaging at postoperative months (POM) 1 and 12. The maximum diameter of the syrinx was measured on mid-sagittal MRI. The extent of tumor resection was categorized as gross total resection (GTR) and subtotal resection (STR).

Results:

The mean age of the 38 patients (22 male and 16 female individuals) was 50.9 years (range, 21–71 y) at the time of surgery. The mean preoperative duration from disease onset was 14.9 months (range, 2–47 mo). GTR was achieved in 28 patients (74%) and STR in 10 (26%). The mean syrinx sizes preoperatively and at POM 1 and POM 12 were 7.5±2.3, 4.1±1.9, and 2.5±1.8 mm, respectively, with significant differences among the time points (P<0.01). The syrinx size shrunk over time after GTR and STR. The shrinkage rate was significantly higher in GTR cases (P<0.05) and in cases with the improvement of McCormick grade for neurological status after both GTR and STR (P<0.05).

Conclusions:

These findings suggest that MRI can be used to evaluate the improvement of neurological status after surgery for spinal ependymoma.
Alectinib following brigatinib: an efficient sequence for the treatment of advanced anaplastic lymphoma kinase-positive lung cancer patients
Authors: Hochmair Maximilian Johannes , Prosch Helmut , Krenbek Dagmar , Weinlinger Christoph , Fabikan Hannah , Valipour Arschang
Published: August 2020

Anaplastic lymphoma kinase (ALK)-translocations are present in up to 5% of non-small cell lung cancer (NSCLC), most of them being adenocarcinomas. Even though the availability of five potent ALK-inhibitors for the treatment of ALK-positive NSCLC patients, there is no consensus about the ideal therapy sequence. Alectinib has been so far successfully and routinely used as first-line therapy, especially in patients presenting central nervous system lesions; however, with the very recent European approval of brigatinib in the first line, a new treatment option is now available for ALK+ patient collective. In this case series, efficient systemic and intracranial responses to alectinib late-line treatment following brigatinib therapy are reported. This therapeutic sequence is going to gain therefore more importance in a near future
Changes in Reverse Transcription Polymerase Chain Reaction–positive Severe Acute Respiratory Syndrome Coronavirus 2 Rates in Adults and Children According to the Epidemic Stages
Authors: Levy Corinne , Basmaci Romain , Bensaid Philippe , Bru Cécile Bost , Coinde Edeline , Dessioux Emmanuelle , Fournial Cécile , Gashignard Jean , Haas Hervé , Hentgen Véronique , Huet Frédéric , Lalande Muriel , Martinot Alain , Pons Charlotte , Romain Anne Sophie , Ursulescu Nicoleta , Le Sage François Vie , Raymond Josette , Béchet Stéphane , Toubiana Julie , Cohen Robert
Published: August 2020

From March 2, 2020, to April 26, 2020, 52,588 reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were performed in France, 6490 in children and 46,098 in adults. The rate of RT-PCR–positive SARS-CoV-2 tests for children (5.9%) was always less than that for adults (20.3%) but vary according to the epidemic stage. The risk ratio of RT-PCR–positive SARS-CoV-2 tests for adults compared with children was 3.5 (95% confidence interval: 3.2–3.9) for the whole study period.
No pain, still gain (of function): the relation between sensory profiles and the presence or absence of self-reported pain in a large multicenter cohort of patients with neuropathy
Authors: Forstenpointner Julia , Ruscheweyh Ruth , Attal Nadine , Baron Ralf , Bouhassira Didier , Enax-Krumova Elena K. , Finnerup Nanna B. , Freynhagen Rainer , Gierthmühlen Janne , Hansson Per , Jensen Troels S. , Maier Christoph , Rice Andrew S.C. , Segerdahl Märta , Tölle Thomas , Treede Rolf-Detlef , Vollert Jan
Published: August 2020

The pathophysiology of pain in neuropathy is complex and may be linked to sensory phenotypes. Quantitative sensory testing, a standardized method to evaluate sensory profiles in response to defined stimuli, assesses functional integrity of small and large nerve fiber afferents and central somatosensory pathways. It has revealed detailed insights into mechanisms of neuropathy, yet it remains unclear if pain directly affects sensory profiles. The main objective of this study was to investigate sensory profiles in patients with various neuropathic conditions, including polyneuropathy, mononeuropathy, and lesions to the central nervous system, in relation to self-reported presence or absence of pain and pain sensitivity using the Pain Sensitivity Questionnaire. A total of 443 patients (332 painful and 111 painless) and 112 healthy participants were investigated. Overall, loss of sensation was equally prevalent in patients with and without spontaneous pain. Pain thresholds were equally lowered in both patient groups, demonstrating that hyperalgesia and allodynia are just as present in patients not reporting any pain. Remarkably, this was similar for dynamic mechanical allodynia. Hypoalgesia was more pronounced in painful polyneuropathy, whereas hyperalgesia was more frequent in painful mononeuropathy (compared with painless conditions). Self-reported pain sensitivity was significantly higher in painful than in painless neuropathic conditions. Our results reveal the presence of hyperalgesia and allodynia in patients with central and peripheral lesions of the somatosensory system not reporting spontaneous pain. This shows that symptoms and signs of hypersensitivity may not necessarily coincide and that painful and painless neuropathic conditions may mechanistically blend into one another.
Factors Affecting Problem Drinking Among Korean Adolescents Based on an Ecological Model
Authors: Cho Mi-Kyoung , Kim Mi Young
Published: August 2020

Purpose

The purpose of this study was to identify the factors affecting problem drinking among adolescents in Korea.

Methods

This survey involved 68,043 adolescents who participated in the Korea Youth Risk Behavior Web-Based Survey conducted in 2015. The data were analyzed using the PASW Statistics 23.0 program.

Results

The subjects were aged 14.96 ± 1.74 years (mean ± standard deviation), including 52.1% male subjects and 53.0% high school students. Most of the drinkers started drinking during their middle school years (13,906 students, 51.6%). Among the 11,021 adolescent drinkers, 7,391 (67.1%) reported at least one of six behavioral problems related to drinking. Problem drinking behaviors involved (a) drinking alcohol to relieve stress; (b) drinking alcohol alone; (c) receiving advice from family or friends to reduce alcohol consumption; (d) driving a motorcycle or riding a bicycle after drinking alcohol, or riding on a motorcycle or a car with a drunk driver at the steering wheel; (e) memory loss after drinking alcohol; and (f) arguing with others after drinking alcohol. The overall problem-drinking score was 1.36 ± 1.42 (range: 0–6). A regression model that included individual (5.7%), interpersonal (3.6%), social (0.3%), contextual (11.7%), and drinking (6.6%) behaviors as predictors accounted for 27.9% of the variance in problem drinking (Wald F = 70.10, p < .001).

Conclusion

The drinking levels as well as method and ease of alcohol purchase were the most significant variables predicting problem drinking by adolescents in Korea.
Point-of-Care Ultrasound Use to Differentiate Hematoma and Sarcoma of the Thigh in the Pediatric Emergency Department
Authors: Le Cathie-Kim , Harvey Gregory , McLean Lianne , Fischer Jason
Published: August 2020

Hematomas and soft tissue sarcomas can be difficult to differentiate clinically, even with the addition of traditional imaging modalities. There are several case reports of sarcomas being misdiagnosed as hematomas, most commonly with a history of mild trauma. In this case report, we described a sarcoma initially misinterpreted as a hematoma on ultrasound. Key clinical features and sonographic findings that may assist clinicians using point-of-care ultrasound to correctly differentiate sarcomas from hematomas are reviewed. A soft tissue mass larger than 5 cm, with internal vascular Doppler flow, presenting without a clear mechanism of injury or with constitutional symptoms should be considered as suspicious for malignancy.
Prevalence of Venous Thromboembolism in Critically-ill COVID-19 Patients: Systematic Review and Meta-analysis
Authors: Mohamed Mouhand F.H. , Al-Shokri Shaikha D. , Shunnar Khaled M. , Mohamed Sara F. , Najim Mostafa S. , Ibrahim Shahd I. , Elewa Hazem , Dousa Khalid M. , Abdalla Lina O. , El-Bardissy Ahmed , Elshafei Mohamed Nabil , Abubeker Ibrahim Y. , Danjuma Mohammed , Yassin Mohamed A
Published: August 2020

Background

Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis. Methods: We performed a systematic review and proportion meta-analysis following PRISMA guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 22/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, we compared the odds of VTE in patients on prophylactic compared to therapeutic anticoagulation. Results: The review comprised of 24 studies and over 2500 patients. The pooled proportion of VTE prevalence was 0.31 (95% CI 0.24, 0.39 I2 94%), of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63 I2 91%), of deep-venous-thrombosis was 0.23 (95% CI 0.14, 0.32 I2 96%), of pulmonary embolism was 0.14 (95% CI 0.09, 0.20 I2 90%). In a subgroup of studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared to therapeutic anticoagulation (OR 5.45; 95% CI 1.90, 15.57 I2 0%). Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages seem to reduce VTE burden in this patient’s cohort compared to standard prophylactic anticoagulation; ongoing randomized controlled trials will further confirm this.
IMPACT OF CONDITIONING INTENSITY AND GENOMICS ON RELAPSE AFTER ALLOGENEIC TRANSPLANTATION FOR PATIENTS WITH MYELODYSPLASTIC SYNDROME
Authors: Dillon Laura W. , Gui Gege , Logan Brent R. , Fei Mingwei , Ghannam Jack , Li Yuesheng , Licon Abel , Alyea Edwin P. , Bashey Asad , Devine Steven M. , Fernandez Hugo F. , Giralt Sergio , Hamadani Mehdi , Howard Alan , Maziarz Richard T. , Porter David L. , Warlick Erica D. , Pasquini Marcelo C. , Scott Bart L. , Horwitz Mitchell E. , Deeg H. Joachim , Hourigan Christopher S.
Published: August 2020

Myelodysplastic Syndrome (MDS) patients are at risk of relapse after allogeneic hematopoietic cell transplantation (alloHCT). The utility of ultra-deep genomic testing to predict, and the impact of conditioning intensity to prevent, MDS relapse are unknown. Targeted error-corrected DNA sequencing was performed on pre-conditioning blood samples from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901 phase III randomized clinical trial which compared outcomes by alloHCT conditioning intensity in adult patients with less than 5% marrow myeloblasts and no leukemic myeloblasts in blood on morphological analysis at the time of pre-transplant assessment. Using a previously described set of 10 gene regions, 42% of patients had mutations detectable prior to randomization to reduced intensity or myeloablative conditioning. Testing positive was associated with increased rates of relapse and decreased overall survival. In those testing positive, relapse rates were higher and relapse-free survival was lower in reduced intensity versus myeloablative conditioning arms. Testing additional genes, including those associated with MDS, did not improve prognostication. This study provides evidence that post-transplant relapse rates in MDS patients are highest in those with pre-transplant genomic evidence of high-risk disease. In those testing positive, randomization to myeloablative conditioning lowered but did not eliminate relapse risk.
Evaluating the direct effects of childhood adiposity on adult systemic-metabolism: A multivariable Mendelian randomization analysis
Authors: Richardson Tom G , Mykkänen Juha , Pahkala Katja , Ala-Korpela Mika , Bell Joshua A , Taylor Kurt , Viikari Jorma , Lehtimäki Terho , Raitakari Olli , Smith George Davey
Published: August 2020

Background

Individuals who are obese in childhood have an elevated risk of cardiometabolic disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independent of adult adiposity, is unclear.

Methods and Results

We conducted a multivariable Mendelian randomization (MR) study to simultaneously evaluate the effects of childhood and adulthood body size on over 100 systemic molecular biomarkers representing multiple metabolic pathways. We first validated UK Biobank-derived genetic risk scores using data on body mass index (BMI) measured during childhood (n=2,427, age: 3-18 years) and adulthood (n= 1,762, age: 34-49 years) from the Young Finns Study (YFS). Results indicated that the childhood score is a stronger predictor of childhood BMI (0.74 vs 0.62 area under the curve (AUC) for the childhood and adult scores respectively), whereas the adult score was a stronger predictor of adulthood BMI (0.57 vs 0.62 AUC). Two-sample MR analyses in a univariable setting using summary genome-wide association study (GWAS) data in up to 24,925 adults provided evidence of an effect of childhood body size on 42 of the 123 metabolic markers assessed (based on P<4.07×10-04). Undertaking multivariable MR analyses suggested that the effects for the majority of these metabolic biomarkers (35/42) substantially attenuated when accounting for adult body size. In further analyses, the biomarkers with the strongest evidence of mediating a long-term effect of adiposity on coronary artery disease (CAD) risk were those related to triglyceride-rich very-low-density lipoprotein particles. In contrast, the biomarkers which showed the strongest evidence of being directly influenced by childhood body size (amino acids leucine, isoleucine and tyrosine) provided little evidence that they mediate this effect on adult disease risk.

Conclusions

The effects of childhood adiposity on the majority of biomarkers investigated in this study were greatly attenuated when accounting for adult body size. This suggests that the detrimental impact of genetically predicted childhood adiposity on systemic metabolism, as well as subsequent later life risk of CAD, can likely be mitigated through lifestyle modifications during adolescence and early adulthood.
Viral shedding and immunological features of children COVID-19 patients
Authors: Yang Yang , Zheng Haixia , Peng Ling , Wei Jinli , Wang Yanrong , Li Hexiao , Peng Bo , Fang Shisong , Zhang Mingxia , Li Yanjie , Liu Hui , Feng Kai , Xing Li , Wang Jun , Cao Mengli , Wang Fuxiang , Liu Lei , Liu Yingxia , Yuan Jing
Published: August 2020

Background

SARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed.

Methods

Epidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines.

Results

40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-α2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1α, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o.

Conclusion

COVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.
Mortality & COVID-19: A Snapshot of a Tertiary Care Facility in Pakistan
Authors: Rana Muhammad Asim , Qayyum Ahad , Hashmi Mubashar , Saif Muhammad Muneeb Ullah , Munir Muhammad Faisal , Pervaiz Rizwan , Hafeez Muhammad Mansoor
Published: August 2020

Introduction

Ever since Sars CoV-2 infection has started from China and has taken the shape of pandemic the mortality associated with this disease has been under discussion and hypercoagubility, acute severe respiratory syndrome and sepsis with multi organ failure have been accursed as possible reasons of deaths in cases infected with novel Corona virus. We conducted a retrospective analysis of the cases admitted in our high dependency and Intensive care unit and tried to pinpoint the major cause of mortality in our cases.

Methods

This is a single center retrospective study carried out at Bahria International Hospital Lahore over a 3 month period (May 10th to July 10th 2020) in which we analyzed the clinical and biochemical profiles of the COVID-19 patients who died during this period.

Results

A total of 108 patients were admitted during this period out of which 11 patients died. 7 of them were men and 4 women. Majority of them had sudden cardiac arrest due to acute coronary syndrome followed by multiorgan dysfunction syndrome and acute respiratory distress syndrome.

Conclusion

Acute coronary syndrome due to hypercoagubility was the leading cause of death in our patients.
Exposure and risk factors for COVID-19 and the impact of staying home on Michigan residents
Authors: Wu Kuan-Han H. , Hornsby Whitney E. , Klunder Bethany , Krause Amelia , Driscoll Anisa , Kulka John , Bickett-Hickok Ryan , Fellows Austin , Graham Sarah , Kaleba Erin O. , Hayek Salim S. , Shi Xu , Sutton Nadia R. , Douville Nicholas , Mukherjee Bhramar , Jamerson Kenneth , Brummett Chad M. , Willer Cristen J.
Published: August 2020

COVID-19 has had a substantial impact on clinical care and lifestyles globally. The State of Michigan reports over 80,000 positive COVID-19 tests between March 1, 2020 and July 29, 2020. We surveyed 8,047 Michigan Medicine biorepository participants in late June 2020. We found that 58% of COVID-19 cases reported no known exposure to family members or to someone outside the house diagnosed with COVID-19. A significantly higher rate of COVID-19 cases were employed as essential workers (45% vs 19%, p=3×10-11). COVID-19 cases reporting a fever were more likely to require hospitalization (categorized as severe; OR = 4.6 [95% CI: 1.7-13.0, p=0.004]) whereas respondents reporting rhinorrhea was less likely to require hospitalization (categorized as mild-to-moderate; OR = 0.16 [95% CI: 0.04-0.70, p=0.016]). African-Americans reported higher rates of being diagnosed with COVID-19 (OR = 4.0 [95% CI: 2.2-7.2, p=1×10-4]), as well as higher rates of exposure to family or someone outside the household diagnosed with COVID-19, an annual household income < $40,000, living in rental housing, and chronic diseases. During the Executive Order in Michigan, African Americans, women, and the lowest income group reported worsening health behaviors and higher overall concern for the potential detrimental effects of the pandemic. The higher risk of contracting COVID-19 observed among African Americans may be due to the increased rates of working as essential employees, lower socioeconomic status, and exposure to known positive cases. Continued efforts should focus on COVID-19 prevention and mitigation strategies, as well as address the inequality gaps that result in higher risks for both short-term and long-term health outcomes.
Differentiated service delivery models for HIV treatment in Malawi, South Africa, and Zambia: A landscape analysis
Authors: Huber Amy , Pascoe Sophie , Nichols Brooke , Long Lawrence , Kuchukhidze Salome , Phiri Bevis , Tchereni Timothy , Rosen Sydney
Published: August 2020

Introduction

Many countries in Africa are scaling up differentiated service delivery (DSD) models for HIV treatment, but most existing data systems do not describe the models in use. We surveyed organizations that were supporting DSD models in 2019 in Malawi, South Africa, and Zambia to describe the diversity of DSD models being implemented at that time.

Methods

We interviewed DSD model implementing organizations for descriptive information about each of the organization’s models of care. We described the key characteristics of each model, including population of patients served, location of service delivery, frequency of interactions with patients, duration of dispensing, and cadre(s) of provider involved. To facilitate analysis, we refer to one organization supporting one model of care as an “organization-model.”.

Results

The 34 respondents (8 in Malawi, 16 in South Africa, 10 in Zambia) interviewed described a total of 110 organization-models, which included 19 facility based individual models, 21 out-of-facility based individual models, 14 healthcare worker led groups, and 3 client led groups; jointly, these encompassed 12 service delivery strategies. Over 2/3 (n=78) of the organization-models were limited to clinically stable patients. Almost all organization-models (n=96) continued to provide clinical care at established healthcare facilities; medication pickup took place at facilities, external pickup points, and adherence clubs. Required numbers of provider interactions per year varied widely, from a low of 2 to a high of 12. Dispensing intervals were typically 3 or 6 months in Malawi and Zambia and 2 months in South Africa. Individual models relied more on clinical staff (doctors, nurses, pharmacists), while group models made greater use of lay personnel (community health workers, counselors).

Conclusions

As of 2019, there was a large variety of differentiated service models being offered for HIV treatment in Malawi, South Africa, and Zambia, serving diverse patient populations.
Changes in back pain scores after bariatric surgery in obese patients: A systematic review and meta-analysis
Authors: Koremans Froukje W. , Chen Xiaolong , Das Abhirup , Diwan Ashish D.
Published: August 2020

STRUCTURED ABSTRACT

Objective

To evaluate if back pain scores in morbidly obese patients change after bariatric surgery.

Summary Background Data

Obese patients often complain of low back pain (LBP), however the underlying mechanism is not fully understood. Recent research shows that, next to mechanical loading, the chronic low-grade inflammation that arises in obese patients is contributing to LBP due to intervertebral disc degeneration. Therefore, it is hypothesized that bariatric surgery will have an effect on the LBP in obese patients.

Methods

We searched four online databases for randomized controlled trials and observational studies. In obese patients, eligible for bariatric surgery, the changes in pre- and postoperative pain scores, assessed by Numeric Rating Pain Scale (NPS) or Visual Analogue Scale (VAS), were considered as primary outcomes. Effect size (ES) and their 95% confidence intervals (CI) were evaluated.

Results

Eight observational studies met the eligibility criteria. All studies showed a reduction of LBP following bariatric surgery, with a mean change of −2.9 points in NPS and of −3.8 cm in VAS. Among the patients undergoing bariatric surgery, based on a fixed effect estimated by pain assessment, the pain score decreased significantly in both groups; in NPS (ES −3.49, 95%CI [−3.86, −3.12]) and in VAS (ES −3.975, 95%CI [−4.45, −3.50]).

Conclusions

From this meta-analysis, the data of back pain improvement following bariatric surgery seems encouraging. Substantial weight loss following bariatric surgery might be associated with a reduction in back pain intensity.
Assembly of bacterial cell division protein FtsZ into dynamic biomolecular condensates
Authors: Robles-Ramos Miguel Ángel , Zorrilla Silvia , Alfonso Carlos , Margolin William , Rivas Germán , Monterroso Begoña
Published: August 2020

Biomolecular condensation through phase separation may be a novel mechanism to regulate bacterial processes, including cell division. Previous work revealed FtsZ, a protein essential for cytokinesis in most bacteria, and theE. colidivision site selection factor SlmA form FtsZ∙SlmA biomolecular condensates. The absence of condensates composed solely of FtsZ under the conditions used in that study suggested this mechanism was restricted to nucleoid occlusion or SlmA-containing bacteria. Here we report that FtsZ alone can demix into condensates in bulk and when encapsulated in synthetic cell-like systems. Condensate assembly depends on FtsZ being in the GDP-bound state and on crowding conditions that promote its oligomerization. FtsZ condensates are dynamic and gradually convert into FtsZ filaments upon GTP addition. Notably, FtsZ lacking its C-terminal disordered region, a structural element likely to favor biomolecular condensation, also forms condensates, albeit less efficiently. The inherent tendency of FtsZ to form condensates susceptible to modulation by physiological factors, including binding partners, suggests that such mechanisms may play a more general role in bacterial cell division than initially envisioned.
A giant cell enhancer achieves cell-type specificity through activation via TCP and repression by Dof transcription factors
Authors: Hong Lilan , Ko Clint S. , Kang S. Earl , Pruneda-Paz Jose L. , Roeder Adrienne H. K.
Published: August 2020

Proper pattern formation relies on the tight coordination of cell fate specification and cell cycle regulation in growing tissues. How this can be organized at enhancers that activate gene expression necessary for differentiation is not well understood. One such example is the patterning of theArabidopsis thalianasepal epidermis where giant cell fate specification is associated with the endoreduplication cell cycle. Previously, we identified an enhancer region capable of driving giant cell-specific expression. In this study, we use the giant cell enhancer as a model to understand the regulatory logic that promotes cell-type specific expression. Our dissection of the enhancer revealed that giant cell specificity is achieved primarily through the combination of two elements: an activator and a repressor. TCP transcription factors are involved in activation of non-specific expression throughout the epidermis with higher expression in endoreduplicated giant cells than small cells. Dof transcription factors act via the second element to repress activity of the enhancer and limit expression to giant cells. Thus, we find that cell-type specific expression emerges from the combined activities of two broadly acting enhancer elements.
SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters
Authors: Mok Bobo Wing-Yee , Cremin Conor J. , Lau Siu-Ying , Deng Shaofeng , Chen Pin , Zhang Anna Jinxia , Lee Andrew Chak-Yiu , Liu Honglian , Liu Siwen , Ng Timothy Ting-Leung , Lao Hiu-Yin , Lee Eddie Lam-Kwong , Leung Kenneth Siu-Sing , Wang Pui , To Kelvin Kai-Wang , Chan Jasper Fuk-Woo , Chan Kwok-Hung , Yuen Kwok-Yung , Siu Gilman Kit-Hang , Chen Honglin
Published: August 2020

SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.