bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of 1 g Ceftriaxone Monotherapy Compared to Dual Therapy With Azithromycin or Doxycycline for Treating Extragenital Gonorrhea Among Men Who Have Sex With Men
Authors: Aoki Takahiro , Mizushima Daisuke , Takano Misao , Ando Naokatsu , Uemura Haruka , Yanagawa Yasuaki , Watanabe Koji , Gatanaga Hiroyuki , Kikuchi Yoshimi , Oka Shinichi
Published: May 2021

Background

Evidence on efficacy of high-dose ceftriaxone monotherapy for extragenital Neisseria gonorrhoeae (NG) infection is lacking.

Methods

A cohort of men who have sex with men (MSM) were tested for NG/Chlamydia trachomatis (CT) every 3 months, in a single-center observational study in Tokyo, Japan. MSM aged > 19 years diagnosed with extragenital NG infection between 2017 and 2020 were included. A single dose of 1 g ceftriaxone monotherapy was provided, while dual therapy with a single oral dose of 1 g azithromycin or 100 mg doxycycline administered orally twice daily for 7 days were given, for those coinfected with CT, according to infected sites. Efficacy of these treatments was calculated by the number of NG-negative subjects at test-of-cure divided by the number of subjects treated. Fisher exact tests were used to compare the efficacy between the 2 groups.

Results

Of 320 cases diagnosed with extragenital NG, 208 were treated with monotherapy and 112 were treated with dual therapy. The efficacy against total, pharyngeal, and rectal infections was 98.1% (204/208, 95% confidence interval [CI]: 95.2–99.3%), 97.8% (135/138, 95% CI: 93.8–99.4%), and 98.6% (69/70, 95% CI: 92.3–99.9%), respectively, in the monotherapy group, whereas the corresponding efficacy in the dual therapy was 95.5% (107/112, 95% CI: 90.0–98.1%), 96.1% (49/51, 95% CI: 86.8–99.3%), and 95.1% (58/61, 95% CI: 86.5–98.7%), respectively. No significant difference in the corresponding efficacy was observed between the two groups (P = .29, P = .61, P = .34, respectively).

Conclusions

High-dose ceftriaxone monotherapy is as effective as dual therapy for extragenital NG among MSM.
Left atrial strain by speckle tracking predicts atrial fibrosis in patients undergoing heart transplantation
Authors: Lisi Matteo , Mandoli Giulia Elena , Cameli Matteo , Pastore Maria Concetta , Righini Francesca Maria , Benfari Giovanni , Rubboli Andrea , D’Ascenzi Flavio , Focardi Marta , Tsioulpas Charilaos , Bernazzali Sonia , Maccherini Massimo , Lisi Edoardo , Lindqvist Per , Valente Serafina , Mondillo Sergio , Henein Michael Y
Published: May 2021

Aims

In patients with heart failure (HF), chronically raised left ventricular (LV) filling pressures lead to progressive left atrial (LA) dysfunction and fibrosis. We aimed to assess the correlation of LA reservoir strain (peak atrial longitudinal strain, PALS) by speckle tracking echocardiography (STE) and LA fibrosis assessed by myocardial biopsy in patients undergoing heart transplantation (HTx).

Methods and results

Forty-eight patients with advanced HF [mean age 51.2 ± 8.1 years, 29% females; LV ejection fraction ≤25% and New York Heart Association (NYHA) class III–IV] referred for HTx were enrolled and underwent pre-operative echocardiographic evaluation, right heart catheterization, and cardiopulmonary exercise testing. Exclusion criteria were non-sinus rhythm, mechanical ventilation, severe mitral/tricuspid regurgitation, or other valvular disease and poor acoustic window. After HTx, LA bioptic samples were collected and analysed to determine the extent of myocardial fibrosis (%). LA fibrosis showed correlation with PALS (R = −0.88, P < 0.0001), VO2max (R = −0.68, P < 0.0001), NYHA class (R = 0.66, P < 0.0001), LA stiffness (R = 0.58, P = 0.0002), and E/e' (R = 0.44, P = 0.005), while poorly correlated with E/A ratio (R = 0.23, P = 0.21). PALS had a good correlation with NYHA class (R = −0.64, P < 0.0001), PAoP (R = −0.61, P = 0.03) and VO2max (R = 0.57, P = 0.0001). Multivariate regression analysis identified PALS (beta = −0.91, P < 0.001) and LA Volume (beta = −0.19, P = 0.03) as predictors of LA Fibrosis, while E/e’ was not a significant predictor (beta = 0.15, P = 0.08).

Conclusion

Emerging as a possible index of myocardial fibrosis in patients with advanced HF, PALS could help to optimize the management and the selection of those patients with irreversible LA structural damage for advanced therapeutic strategies.
A case report of successful intravascular shockwave lithotripsy andad hocdirectional venous atherectomy of extensive chronic femoral deep venous thrombosis
Authors: Agrawal Yashwant , Ponna Pramod , Zoltowska Dominika M , Halabi Abdul R
Published: May 2021

Background

Conventional treatment for chronic deep venous thrombosis (DVT) is anticoagulation. However, limited interventional endovascular options exist for patients with non-healing venous ulcers secondary to chronic DVT.

Case summary

We present a case of 67-year-old man with severely symptomatic post-thrombotic syndrome (PTS) with persistent high-grade femoral DVT despite prior compressive therapy and chronic oral anticoagulation. It has been successfully treated with intravascular shockwave lithotripsy and ad hoc directional venous atherectomy facilitating subsequent mechanical thrombectomy and venoplasty. The procedure was without complication and resulted in significant clinical improvement.

Discussion

We believe our novel endovascular interventional approach represents a unique modality of intervention for patients with chronic DVT and PTS resistant to conventional venoplasty.
Interventricular septum mass presenting as a late acute coronary syndrome with ST-segment elevation: a case report
Authors: Coroyer Lucas , Garcon Philippe , Duchatelle Veronique , Azarine Arshid
Published: May 2021

Background

Intracardiac masses are relatively rare but the diagnosis can be challenging for the cardiologist and the clinical presentation can be misleading. While most of the cardiac masses are benign, malignant masses are mostly metastatic tumours.

Case summary

An 81-year-old man was admitted to the cardiology department for congestive heart failure with the complaint of recent dyspnoea. The initial electrocardiogram was suggestive of a late presentation of an anterior myocardial infarction. Blood test showed mild and stable elevation of troponin and brain natriuretic peptide. Doppler-echocardiography revealed an interventricular septal thickening. Contrast echocardiography revealed a mass with a possibly necrotic centre and peripheral hypervascularization. Cardiac computed tomography (CT) confirmed the existence of a cardiac tumour with a hypodense centre and also revealed the presence of a large tumour of the lung’s left lower lobe with multiple enlarged lymph nodes associated with possible left adrenal gland metastasis. Computed tomography-guided percutaneous biopsy of the pulmonary mass demonstrated a squamous cell lung cancer which was likely the primary cancer. The patient was discharged home waiting for chemotherapy to start but died a few days later at home of an unknown cause.

Discussion

Diagnosis of intracardiac mass is difficult, often requiring multiple imaging modalities. Contrast-enhanced echocardiography may help early diagnosis and can be easily implemented with other imaging modalities such as cardiac magnetic resonance imaging or CT.
Successful implantation of a leadless pacemaker in a patient with complete atrioventricular block and congenital absence of superior vena cava: a case report
Authors: Kawaguchi Taiyo , Yatsu Shoichiro , Shiozawa Tomoyuki , Suwa Satoru
Published: May 2021

Background

Congenital absence of superior vena cava (CASVC) is an extremely rare vascular anomaly often associated with conduction disturbances which makes implantation of a pacemaker difficult. We report a case of pacemaker implantation in a patient presenting with complete atrioventricular block (c-AVB) with bilateral absence of the SVC.

Case summary

A 68-year-old man who had experienced dyspnoea on exertion by c-AVB was admitted to our hospital for treatment and management. Permanent pacemaker insertion was initially planned; however, an endocardial pacemaker lead could not be implanted in the right atrium. Computed tomography scan with contrast revealed that the venous blood from the upper half of the body flowed into the inferior vena cava via the azygos vein. Due to the difficulty of inserting an endocardial lead from the subclavian vein, a leadless pacemaker (LP) was implanted instead via the femoral vein.

Discussion

This is the first case of an LP implantation in a patient presenting with c-AVB with CASVC. Confirmation of blood vessel anatomy to rule out CASVC is necessary prior to pacemaker implantation when abnormal venous anatomy is suspected.
Statin but not aspirin treatment is associated with reduced cardiovascular risk in patients with diabetes without obstructive coronary artery disease: a cohort study from the Western Denmark Heart Registry
Authors: Olesen Kevin Kris Warnakula , Heide-Jørgensen Uffe , Thim Troels , Thomsen Reimar W , Bøtker Hans Erik , Sørensen Henrik T , Maeng Michael
Published: May 2021

Aims

Patients with diabetes and no obstructive coronary artery disease (CAD) as assessed by coronary angiography (CAG) are frequently treated with aspirin and statins. We examined the effectiveness of aspirin and statin treatment on cardiovascular and bleeding incidence in patients with diabetes and absent obstructive CAD.

Methods and results

The study included patients with diabetes and absent obstructive CAD as assessed by CAG from 2003 to 2016 in Western Denmark. We stratified patients by aspirin and statin treatment within 6 months after CAG in two separate analyses. Outcomes were MACE (major adverse cardiovascular events, a composite of myocardial infarction, ischaemic stroke, and death) and bleeding (aspirin only). To account for confounding, we used propensity score-based weights to estimate the inverse probability of treatment-weighted hazard ratios (HRIPTW). We included 4124 patients with diabetes but without CAD as assessed by CAG, among whom 2474 (60%) received aspirin and 2916 (71%) received statin treatment within 6 months following CAG. Median follow-up was 4.9 years. Aspirin did not reduce 10-year MACE [21.3% vs. 21.8%, HRIPTW 1.01, 95% confidence interval (CI) 0.82–1.25], all-cause death (HRIPTW 0.96, 95% CI 0.74–1.23), or bleeding (HRIPTW 0.95, 95% CI 0.73–1.23), compared to those not receiving aspirin treatment. Statin treatment reduced MACE (25% vs. 37%, HRIPTW 0.58, 95% CI 0.48–0.70) compared to those not receiving statin treatment.

Conclusion

Among patients with diabetes and no obstructive CAD, aspirin neither reduced MACE nor increased bleeding. In contrast, statin treatment was associated with a major reduction in risk of MACE.
pSONIC: Ploidy-aware Syntenic Orthologous Networks Identified via Collinearity
Authors: Conover Justin L , Sharbrough Joel , Wendel Jonathan F
Published: May 2021

With the rapid rise in availability of high-quality genomes for closely related species, methods for orthology inference that incorporate synteny are increasingly useful. Polyploidy perturbs the 1:1 expected frequencies of orthologs between two species, complicating the identification of orthologs. Here we present a method of ortholog inference, Ploidy-aware Syntenic Orthologous Networks Identified via Collinearity (pSONIC). We demonstrate the utility of pSONIC using four species in the cotton tribe (Gossypieae), including one allopolyploid, and place between 75% and 90% of genes from each species into nearly 32,000 orthologous groups, 97% of which consist of at most singletons or tandemly duplicated genes—58.8% more than comparable methods that do not incorporate synteny. We show that 99% of singleton gene groups follow the expected tree topology and that our ploidy-aware algorithm recovers 97.5% identical groups when compared to splitting the allopolyploid into its two respective subgenomes, treating each as separate “species.”
Tail Autotomy Alters Prey Capture Performance and Kinematics, but not Success, in Banded Geckos
Authors: Vollin Marina F , Higham Timothy E
Published: May 2021

Tails are versatile structures with diverse forms and functions across vertebrates. They are involved in almost all behaviors critical to survival including locomotion, feeding, and predator avoidance. Although the tail’s role in locomotion and stability has been widely studied, its role in prey capture is relatively unknown. Lizards are an ideal system to examine the tail’s impact on prey capture as most are capable of autotomizing, or dropping, their tail in response to predation and intraspecific competition. Tail autotomy can lower reproduction, decrease locomotor performance, impart instability during jumping, and decrease social status. Desert banded geckos (Coleonyx variegatus) frequently capture evasive prey in nature and appear to use their tail during strikes. However, it is unclear if these tail movements are important for the strike itself, or if they simply draw attention to that part of the body. We used high-speed 3D videography to quantify prey capture performance and kinematics of C. variegatus striking at crickets before and after total caudal autotomy. Trials were conducted within 2 h of autotomy and then repeatedly over a 2-week period. Overall, prey capture success was unaffected by caudal autotomy. However, maximum strike velocity decreased significantly after autotomy, highlighting the importance of the tail during prey capture. Strike kinematics were altered after autotomy in several ways, including geckos adopting a more sprawled posture. Maximum pectoral girdle and mid-back height were significantly lower during post-autotomy strikes, whereas maximum pelvic girdle height was unaffected. However, individual variation was considerable. This downward pitching of the body after tail loss suggests that the tail is necessary for counterbalancing the anterior portion of the body and resisting the rotational inertia incurred after pushing off with the hindlimbs. Utilizing autotomy to test tail function in prey capture can provide valuable insight into how the tail is used in terrestrial predation across a wide variety of species and ecological niches.
Metformin acts to suppress β-hydroxybutyric acid-mediated inflammatory responses through activation of AMPK signaling in bovine hepatocytes
Authors: Xu Tianle , Lu Xubin , Arbab Abdelaziz Adam Idriss , Wu Xinyue , Mao Yongjiang , Loor Juan J , Yang Zhangping
Published: May 2021

The occurrence of bovine ketosis involves the accumulation of β-hydroxybutyric acid (BHBA), which contributes to the initiation and acceleration of hepatic metabolic stress and inflammation. Metformin has other beneficial effects apart from its medical intervention for diabetes, such as prevention of laminitis and hyper-triglyceridemic. AMPK maintains energy homeostasis and is the intracellular target of metformin action. This study aims to uncover the role of metformin in modulating BHBA-induced inflammatory responses through the activation of AMPK signaling. The hepatocytes were isolated from the liver tissue of mid-lactation multiparous Holstein cows (~160 d postpartum). Treatments were conducted as follows: treated with PBS for 18 h (control); pretreated with PBS for 12 h followed by treatment of 1.2 mM BHBA for 6 h (BHBA); pretreated with 1.5 mM or 3 mM metformin for 12 h followed by the BHBA treatment (1.2 mM) for 6 h (M(1.5)+B; M(3)+B). The inhibitor of AMPK, Compound C, at a concentration of 10 μM, was applied to substantiate the AMPK-dependent responses. RT-qPCR were applied for the mRNA expression while Western-blots and immunofluorescence were conducted for the target proteins expression. Among dose-dependent assays for BHBA, the concentration of BHBA at 1.2 mM activated NF-κB signaling by upregulating the expression of phosphorylated NF-κB and pro-inflammatory cytokines compared with the control cells (P < 0.05). Along with the upregulation of phosphorylated AMPKα and ACCα, metformin at 1.5 and 3 mM inactivated NF-κB signaling components (p65 and IκBα) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA. Additionally, BHBA inhibited cells staining intensity in EdU assay were increased by pretreatment with metformin. The activation of AMPK resulted in the increased gene and protein expression of SIRT1, along with the deacetylation of H3K9 and H3K14. However, the AMPK inhibitor compound C blocked this effect. Compared with BHBA treated cells, the protein expression of COX-2 and IL-1β were decreased by the pretreatment with metformin, and the inhibitory effect of metformin was released by compound C. The bound of NF-κB onto IL1B promoter displayed higher in BHBA group and this was suppressed by pretreatment with metformin (P < 0.05). Altogether, metformin attenuates the BHBA-induced inflammation through the inactivation of NF-κB as a target for AMPK/SIRT1 signaling in bovine hepatocytes.
Impact of manganese amino acid complex on tissue-specific trace mineral distribution and corpus luteum function in gilts
Authors: Studer Jamie M , Kiefer Zoe E , Goetz Brady M , Keating Aileen F , Baumgard Lance H , Rambo Zachary J , Schweer Wesley P , Wilson Mark E , Rapp Christof , Ross Jason W
Published: May 2021

Functional corpora lutea (CL) are required for pregnancy establishment and gestational maintenance in swine, and CL function is susceptible to environmental influences. Manganese (Mn) could be critical in regulating CL function since it is a component of the antioxidant enzyme Mn superoxide dismutase (MnSOD) as well as enzymes involved in cholesterol and steroid hormone synthesis. We hypothesized that a more bioavailable dietary Mn source would increase Mn content in the CL thereby influencing luteal function during the mid-luteal phase of the estrous cycle. Postpubertal gilts (n = 32) were assigned to one of four gestation diets. The control diet (CON) met or exceeded National Research Council (2012) requirements and was formulated to contain 20 parts per million (ppm) of added Mn in the form of Mn sulfate. Three additional diets included 20 (treatment [TRT]1), 40 (TRT2), or 60 (TRT3) ppm of added Mn from a Mn–amino acid complex (Availa-Mn; Zinpro Corporation) instead of Mn sulfate. Dietary treatment began at estrus synchronization onset and continued through 12 days post estrus (dpe) of the ensuing estrous cycle. Blood samples were collected at estrus onset, which was assigned as 0 dpe, as well as 4, 8, and 12 dpe. Gilts were euthanized and tissues were collected at 12 dpe. Serum progesterone (P4) increased (P < 0.01) from 0 to 12 dpe but was unaffected by dietary treatment (P = 0.15) and there was no effect of the interaction between day and treatment (P = 0.85). Luteal Mn content increased (P ≤ 0.05) by 19%, 21%, and 24% in gilts fed TRT1, TRT2, and TRT3, respectively, compared to CON. Luteal P4 concentrations decreased (P = 0.03) 25%, 26%, and 32% in gilts fed TRT1, TRT2, and TRT3, respectively, compared to CON. Relative to CON gilts, CL calcium content decreased (P = 0.02) by 36%, 24%, and 34% for TRT1, TRT2, and TRT3 gilts, respectively. Collectively, these data support the hypothesis that feeding a more bioavailable Mn source increases Mn accumulation in CL tissue. If and how this influences CL function may be related to altered luteal P4 concentrations.
Blueberry Yields Increase With Bee Visitation Rates, but Bee Visitation Rates are not Consistently Predicted by Colony Stocking Densities
Authors: Mallinger Rachel , Ternest John J , Naranjo Shiala Morales
Published: May 2021

Pollinator-dependent crops rely on the activity of managed and wild pollinators. While farm management and surrounding landscape can influence wild pollinator contributions, managed pollinator contributions may be primarily driven by their stocking densities, though this is not well studied across crops. We selected 20 southern highbush blueberry farms along two independent gradients of honey bee Apis mellifera L. (Hymenoptera: Apidae) stocking density (~1–11 hives/acre) and bumble bee Bombus impatiens Cresson (Hymenoptera: Apidae) stocking density (0 - 3 colonies/acre) ensuring that stocking densities were not correlated with farm or landscape attributes. Across farms, we observed managed and wild bee visitation rates, and measured yield estimates. Farms with greater bumble bee stocking densities had higher bumble bee visitation rates and yield estimates, but farms with higher honey bee stocking densities only received higher honey bee visitation rates at the end of bloom and did not have higher yield estimates. The main wild pollinator, the southeastern blueberry bee Habropoda laboriosa (Fabricius) (Hymenoptera: Apidae), showed higher visitation rates on organic farms and in late bloom. In general, higher visitation rates by honey bees, bumble bees, and H. laboriosa were correlated with higher yields. Our results suggest that yields are limited by bee visitation rates, and that within the stocking density ranges studied, increasing managed bumble bees, but not honey bees, increases their visitation rates. While H. laboriosa had the greatest effect on yield estimates, its activity appears to be limited by both a phenological mismatch with crop bloom and farm management.
Predictors of hospitalization in patients with rheumatic disease and COVID-19 in Ireland: data from the COVID-19 global rheumatology alliance registry
Authors: Conway Richard , Nikiphorou Elena , Demetriou Christiana A , Low Candice , Leamy Kelly , Ryan John G , Kavanagh Ronan , Fraser Alexander D , Carey John J , O’Connell Paul , Flood Rachael M , Mullan Ronan H , Kane David J , Robinson Philip C , Liew Jean W , Grainger Rebecca , McCarthy Geraldine M ,   for the COVID-19 Global Rheumatology Alliance
Published: May 2021

Objectives

Given the limited data regarding the risk of hospitalization in patients with rheumatic disease and coronavirus disease 2019 (COVID-19) in Ireland, we used the COVID-19 Global Rheumatology Alliance (GRA) registry data to study outcomes and their predictors. The primary objective was to explore potential predictors of hospitalization.

Methods

We examined data on patients and their disease-related characteristics entered in the COVID-19 GRA provider registry from Ireland (from 24 March 2020 to 31 August 2020). Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with hospitalization.

Results

Of 105 patients, 47 (45.6%) were hospitalized and 10 (9.5%) died. Multivariable logistic regression analysis showed that age [odds ratio (OR) = 1.06, 95% CI 1.01, 1.10], number of co-morbidities (OR = 1.93, 95% CI 1.11, 3.35) and glucocorticoid use (OR = 15.01, 95% CI 1.77, 127.16) were significantly associated with hospitalization. A diagnosis of inflammatory arthritis was associated with lower odds of hospitalization (OR = 0.09, 95% CI 0.02, 0.32).

Conclusion

Increasing age, co-morbidity burden and glucocorticoid use were associated with hospitalization, whereas a diagnosis of inflammatory arthritis was associated with lower odds of hospitalization.
Switching between worlds apart: Negotiating European space sector cultures through innovation
Authors: Clormann Michael
Published: May 2021

With the advent of the so-called New Space Age, promoted by private actors and driven by market logic innovation, the European space sector meets significant challenges over recent years. This article explores the implications of New Space’s emergence for contemporary societies that increasingly rely on space technologies as critical infrastructures. It does so by analyzing conflicting logics of innovation within the sector arising from a clash of Old Space and New Space cultures and associated role identities. To this end, it combines concepts of institutional culture and role identity from science and technology studies and organization studies. Tracing the identity work performed by members of the European space sector through qualitative interviews, it concludes that new demands of market logic innovation are negotiated within a mode of switching between different sector cultures. It concludes that this mode provides opportunities for the responsible future governance of critical space infrastructures.
Assessment of the reproductive performances of native sows in Southern Benin
Authors: Djimènou David , Adoligbé Camus M , Aboh André B , Amagnidé Aubin G , Osei-Amponsah Richard , Edénakpo Aimé K , Tobada Pamphile C , Koudandé Delphin O
Published: May 2021

Native sows contribute to a large extent to food security and poverty alleviation in Benin. However, their reproductive performance particularly under extensive systems is poorly characterized. The objective of this study was to fill this knowledge gap by selecting 284 multiparous sows based on hair color and some reproductive parameters. The results showed that native sows of Southern Benin can be clustered into three groups with group 3 showing the best reproductive performances including highest average litter size (LS, 10.31 piglets), live-born piglets (LBP, 10.31 piglets), number of functional teats (10.94), and shorter average farrowing interval (6 mo). The analysis of sows’ performances based on their origin revealed that sows from agro-ecological zone 8 have the highest number of LBP and the lowest age at first mating and first farrowing. The analysis of sows’ performances based on the hair color showed that those with black hair have the largest LS and the highest number of LBP. This study showed that Benin’s native sows have good reproductive ability with enough variation to develop a sustainable pig industry for a better contribution to food security and wealth creation.
Soybean Microbiome Recovery After Disruption is Modulated by the Seed and Not the Soil Microbiome
Authors: Moroenyane Itumeleng , Tremblay Julien , Yergeau Étienne
Published: May 2021

Endophytic microbiomes of healthy seed form a symbiotic relationship with their host. Seed and environment are sources of microbes that colonize the developing plant; however, the influence of each remains unclear. Here, using irradiation combined with surface sterilization to generate near-axenic seed with disrupted and reduced microbiomes, we contrasted the colonization potential of seed and soil microbiomes. We hypothesized that the seed microbiome would be the primary colonizer of the plant endophytic compartments. Our experimental design comprised four treatments, using soybean as a model plant: (i) nearly axenic seed growing in a sterile environment, (ii) nonaxenic seed inoculated with a microbial soil extract, (iii) nearly axenic seed inoculated with a microbial seed extract, and (iv) nearly axenic seed inoculated with a microbial soil extract. After 14 days of growth, plants were harvested, and DNA was extracted from the shoot, roots, and rhizosphere and subjected to 16S ribosomal RNA gene amplicon sequencing, quantitative PCR quantification of the total community, and functional genes involved in the N cycle. Community dynamics were similar for most treatments within their respective compartments, except for the soil treatment, where rhizosphere and root microbiomes differed from other treatments, suggesting that the soil microbiome colonizes the belowground compartment efficiently only when the seed microbiome is severely disrupted. For the shoot, all treatments resembled the seed microbiome treatment, suggesting that the seedborne bacteria colonize the aboveground compartment preferentially. Our results highlight the primacy of the seed microbiome over the soils during early colonization, putting seed microbes as potential candidates of microbiome engineering efforts.
Transforming Disruption Into Innovation: A Partnership Between the COVID-19 Medical Student Response Team and the University of British Columbia
Authors: Tsang Vivian W.L. , Yu Alec , Haines Morgan J. , Sagorin Zach , Mitchell Devon , Ching Geoffrey , Holmes Cheryl L. , Kestler Mary
Published: May 2021

The COVID-19 pandemic caused substantial disruptions in medical education. The University of British Columbia (UBC) MD Undergraduate Program (MDUP) is the sixth-largest medical school in North America. MDUP students and faculty developed a joint response to these disruptions to address the curriculum and public health challenges that the pandemic posed.

After clinical activities were suspended in March 2020, third- and fourth-year MDUP students formed a COVID-19 Medical Student Response Team (MSRT) to support frontline physicians, public health agencies, and community members affected by the pandemic. A nimble organizational structure was developed across 4 UBC campuses to ensure a rapid response to meet physician and community needs. Support from the faculty ensured the activities were safe for the public, patients, and students and facilitated the provision of curricular credit for volunteer activities meeting academic criteria.

As of June 19, 2020, more than 700 medical students had signed up to participate in 68 projects. The majority of students participated in projects supporting the health care system, including performing contact tracing, staffing public COVID-19 call centers, distributing personal protective equipment, and creating educational multimedia products. Many initiatives have been integrated into the MDUP curriculum as scholarly activities or paraclinical electives for which academic credit is awarded. This was made possible by the inherent flexibility of the MDUP curriculum and a strong existing partnership between students and faculty.

Through this process, medical students were able to develop fundamental leadership, advocacy, communication, and collaboration skills, essential competencies for graduating physicians. In developing a transparent, accountable, and inclusive organization, students were able to effectively meet community needs during a crisis and create a sustainable and democratic structure capable of responding to future emergencies. Open dialogue between the MSRT and the faculty allowed for collaborative problem solving and the opportunity to transform disruption into academic innovation.
Characteristics, Comorbidities, Complications, and Outcomes Among 802 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 in a Community Hospital in Florida
Authors: Patel Sachin R. , Mukkera Satyanarayana R. , Tucker Lara , Vatsis Catherine , Poma Antonia , Ammar Ali , Vo Mai , Khan Rumi , Carlan Stephen
Published: May 2021

Objectives:

Coronavirus disease 2019 continues to increase throughout the United States. Despite the rapid progression of the disease, there is limited information of the factors associated with mortality in Florida. This study aims to review the demographics, characteristics, comorbidities, complications, and outcomes of hospitalized patients, and their association with mortality.

Design:

Cohort study.

Setting:

A community-based tertiary-care hospital of Orlando Health, Orlando Regional Medical Center.

Patients/Subjects:

Data of hospitalized patients who tested positive for severe acute respiratory syndrome coronavirus 2 between March 1, 2020, and August 31, 2020, at the Orlando Regional Medical Center.

Interventions:

None.

Measurements and Main Results:

Main data assessed included patient demographics, clinical characteristics, comorbidities, complications, outcomes, and inhospital mortality. The median age for hospitalized patients was 61 years; among them, 56% were males. Most were of African American (n = 288, 35.9%), Hispanic (n = 237, 29.6%), and Caucasian (n = 217, 27.1%) descent. More patients presented with symptoms developing at home (n = 589, 75.9%) than from skilled nursing and long-term acute care facilities. The most common comorbidities were diabetes mellitus (42.8%), obesity (39.2%), lung disease (23.3%), coronary artery disease (20.2%), and congestive heart failure (18.3%). Complications with higher odds of mortality were mechanical ventilation (odds ratio, 148.00, p < 0.001), coinfections (odds ratio, 56.42, p < 0.001), acute kidney injury (odds ratio, 84.01, p < 0.001), atrial fibrillation (odds ratio, 28.30, p < 0.001), acute myocardial infarction (odds ratio, 23.29, p < 0.001), and acute venous thromboembolism (odds ratio, 26.43, p < 0.001).

Conclusions:

We identified an increase of severity of coronavirus disease 2019 within older patients of African American and Hispanic descent with comorbidities such as diabetes, coronary artery disease, congestive heart failure, chronic kidney disease, cancer, liver disease, or cerebrovascular disease. Noninvasive positive-pressure ventilation and high-flow nasal cannula oxygen may have helped avert mechanical ventilation, and this may have improved patient outcomes over the course of the study period.
Cutaneous Reconstruction of the Nasal Distal Third: Alternative Local Flaps for a Complex Region
Authors: Cason Roger W. , Shammas, Ronnie L. , Pyfer Bryan J. , Glener Adam D. , Marcus Jeffrey R. , Cook Jonathan L.
Published: May 2021

Small-to-medium cutaneous defects of the distal nose pose a significant challenge to reconstructive surgeons, and commonly described reconstructive techniques have their limitations. As the skin of this region is characteristically rigid and sebaceous, care must be taken to avoid introducing unfavorable tension vectors that can result in functional or anatomic distortion of the nasal free margins. With this in mind, the authors discuss 3 alternative reconstructive options, the East-West, nasalis sling, and trilobed flaps, which have wide utility in the repair of distal nasal cutaneous defects and can result in excellent cosmesis. The indications, surgical technique, and limitations of each are discussed in detail, and are compared with several of the more commonly described options in the context of distal nasal reconstruction.
Analysis of traditional Korean soybean pastes
‘Doenjang’ prepared by processing methods obtained from
ancient documents
Authors: Nam Dong-Geon , Kim Ji-Hyun
Published: May 2021

The purpose of this study was to evaluate the amino acid score and quality
characteristics of commercial (CCT, ‘C’ Co., Ltd.; CDT,
‘D’ Co., Ltd.; and CKT, ‘K’ Co., Ltd.) and
traditional (CJS, Chunsie; NJ, Nanjang; CJ, Chungjang; NCJ, Nan-chungjang; and
GCJ, Gihwa-chungjang) ‘Doenjang’ samples, and to compare the
correlation between the manufacturing methods and quality characteristics.
Variations in pH, titratable acidity, salinity, and reducing sugar (RS) content
were observed among the samples. The total essential amino acid (TEAA) contents
were 254.93–1,777.79 mg/100 g, while glutamic acid was most abundant in the CKT
sample as 2,423.41 mg/100 g. The protein-digestibility-corrected amino acid
score was 0.49 for CSJ. Some commercial and traditional ‘Doenjang’
samples showed high total polyphenol content (GCJ, 2.59%),
2,2-dipenyl-1-picrylhydrazyl radical scavenging capacity (CDT, 19.84 mg AA eq/g;
GCJ, 19.63 mg AA eq/g), and 2,2'-azino-bis
(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging capacity (NCJ, 64.55
mg AA eq/g). The manufacturing method of ‘Doenjang’, pH, acidity,
and salinity were positively correlated (p<0.05; p<0.01), whereas
the manufacturing method of ‘Doenjang’, RS, and TEAA were
negatively correlated (p<0.01). These results provide information
regarding the quality characteristics for the selection of suitable traditional
methods to produce high-quality ‘Doenjang’.
Exploring real-world concordance of tissue mutation burden (TMB) from blood and tissue in patients with solid tumors
Authors: Park Jewel , Park Inae , Hwang Jin Young , Bae William Han , Nam Myungwoo , Lee Grace , Kim Leeseul , Choi Yoonhee , Jung Hojung , Kim Min Jeong , Hong Seung Pyo Daniel , Lee Hiwon , Park Younggyeong , Yu Emma , Lee Alice , Chae Young Kwang
Published: May 2021

Purpose

Tumor mutational burden (TMB) is an approved biomarker for immunotherapy in metastatic cancer patients. While initially measured from tissue (tTMB), TMB derived from circulating tumor DNA (ctDNA) - also known as blood TMB (bTMB) - is increasingly being used in the clinic. Currently, real-world concordance between tTMB and bTMB is not well understood.

Patients and methods

From October 2020 to March 2021, cancer patients who had both tTMB and bTMB results were selected. Patients were classified according to clinical variables and tumor burden, and correlation analyses or tests of independence were performed to explore any associations.

Results

From a total of 38 patients included in our study, 20 patients (52.6%) had non-small cell lung carcinoma and 18 (47.4%) had other cancers. Median bTMB of 9.6 mut/MB was higher than median tTMB of 4.0 mut/Mb, and the distributions of bTMB and tTMB differed significantly (n=38, p < 0.001). bTMB was positively correlated with tTMB in the total study population (Spearman ρ=0.57, p < 0.001) and a tTMB of 10 mut/Mb correlated with a bTMB of 21.1 mut/Mb. Dividing patients by cancer type or site of tumor biopsy resulted in significantly differing strength and degree of correlation, but dividing patients by concordant and discordant bTMB:tTMB ratio did not reveal any significantly different distributions of clinical variables or tumor burden.

Conclusion

bTMB was positively correlated with tTMB, and median bTMB was higher than median tTMB. Cancer type and site of tissue biopsy may influence concordance between tTMB and bTMB. Future studies with more patients may help define the optimal bTMB threshold for receiving immunotherapy, which may be different from the tTMB threshold.
Optimal control of the spatial allocation of COVID-19 vaccines: Italy as a case study
Authors: Lemaitre Joseph C. , Pasetto Damiano , Zanon Mario , Bertuzzo Enrico , Mari Lorenzo , Miccoli Stefano , Casagrandi Renato , Gatto Marino , Rinaldo Andrea
Published: May 2021

While SARS-CoV-2 vaccine distribution campaigns are underway across the world, communities face the challenge of a fair and effective distribution of limited supplies. We wonder whether suitable spatial allocation strategies might significantly improve a campaign’s efficacy in averting damaging outcomes. To that end, we address the problem of optimal control of COVID-19 vaccinations in a country-wide geographic and epidemiological context characterized by strong spatial heterogeneities in transmission rate and disease history. We seek the vaccine allocation strategies in space and time that minimize the number of infections in a prescribed time horizon. We examine scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021, generated by a spatially explicit compartmental COVID-19 model tailored to the Italian geographic and epidemiological context. We propose a novel optimal control framework to derive optimal vaccination strategies given the epidemiological projections and constraints on vaccine supply and distribution logistic. Optimal schemes significantly outperform the explored alternative allocation strategies based on incidence, population distribution, or prevalence of susceptibles in each province. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities imply highly non-trivial prioritization of local vaccination campaigns. The extent of the overall improvements in the objectives grants further inquiry aimed at refining other possibly relevant factors so far neglected. Our work thus provides a proof-of-concept of the potential of optimal control for complex and heterogeneous epidemiological contexts at country, and possibly global, scales.

Author summary

The development of vaccines has sparked high hopes towards the control of SARS-CoV-2 transmission without resorting to extensive community-wide restrictions. A fundamental unanswered question concerns the best possible allocation of a limited vaccine stock in space and time given a specific goal. We address this through an optimal control framework based on a reliable spatially explicit COVID-19 epidemiological model, where vaccine distribution is optimized under supply and deployment capacity constraints. This tool provides strategies for optimal allocations in different scenarios, yielding important improvements over considered alternatives. By accounting for spatial heterogeneities and human mobility networks, the presented approach complements currently used allocation methods based on criteria such as age or risk.
An evidence-based data science perspective on the prediction of heart failure readmissions
Authors: Locey Kenneth J. , Webb Thomas A. , Hota Bala
Published: May 2021

The prevention of unplanned 30-day readmissions of patients discharged with a diagnosis of heart failure (HF) remains a profound challenge among hospital enterprises. Despite the many models and indices developed to predict which HF patients will readmit for any unplanned cause within 30 days, predictive success has been meager. Using simulations of HF readmission models and the diagnostics most often used to evaluate them (C-statistics, ROC curves), we demonstrate common factors that have contributed to the lack of predictive success among studies. We reveal a greater need for precision and alternative metrics such as partial C-statistics and precision-recall curves and demonstrate via simulations how those tools can be used to better gauge predictive success. We suggest how studies can improve their applicability to hospitals and call for a greater understanding of the uncertainty underlying 30-day all-cause HF readmission. Finally, using insights from sampling theory, we suggest a novel uncertainty-based perspective for predicting readmissions and non-readmissions.
High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy in Leishmania donovani
Authors: Negreira Gabriel H. , Monsieurs Pieter , Imamura Hideo , Maes Ilse , Kuk Nada , Yagoubat Akila , Van den Broeck Frederik , Sterkers Yvon , Dujardin Jean-Claude , Domagalska Malgorzata A.
Published: May 2021

Leishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA), might have important evolutionary and functional implications but remains under-explored due to technological limitations. Here, we applied and validated a high throughput single-cell genome sequencing method to study for the first time the extent and dynamics of whole karyotype heterogeneity in two Leishmania clonal populations representing different stages of MA evolution in vitro. We found that drastic changes in karyotypes quickly emerge in a population stemming from an almost euploid founder cell. This possibly involves polyploidization/hybridization at an early stage of population expansion, followed by assorted ploidy reduction. During further stages of expansion, MA increases by moderate and gradual karyotypic alterations. MA usually affected a defined subset of chromosomes, of which some display an enrichment in snoRNA genes which could represent an adaptative benefit to the amplification of these chromosomes. Our data provide the first complete characterization of MA in Leishmania and pave the way for further functional studies.

Note to the BioRxiv community

The present preprint is a revision of an older preprint posted on 06th March 2020 on BioRxiv (https://www.biorxiv.org/content/10.1101/2020.03.05.976233v1). Here we included two extra samples in our single-cell genome sequencing (SCGS) analysis – the BPK081 cl8 clone (a nearly euploid strain) and a population consisting of a mixture of four L. donovani strains which was used as control for high levels of mosaicism in aneuploidy and for estimation of doublets. We also upgraded the bioinformatics pipeline to determine single-cell karyotypes and performed new fluorescence in situ hybridization (FISH) analysis. The new findings observed especially in the BPK081 cl8 led to a reformulation of the text, a new hypothesis for the evolution of mosaicism and a general restructuring of the article. Therefore, the older preprint is obsolete.
Cannabinoid tetrad effects of oral Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in male and female rats: sex, dose-effects and time course evaluations
Authors: Moore Catherine F. , Weerts Elise M.
Published: May 2021

Rationale The legalization of medicinal use of Cannabis sativa in most US states and the removal of hemp from the Drug Enforcement Agency (DEA) controlled substances act has resulted in a proliferation of products containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for oral consumption (e.g., edibles, oils and tinctures) that are being used for recreational and medicinal purposes. Objective This study examined the effects of cannabinoids THC and CBD when administered orally on measures of pain sensitivity, body temperature, locomotor activity, and catalepsy (i.e., cannabinoid tetrad) in male and female Sprague Dawley rats. Methods Rats (N=24, 6 per sex/drug group) were administered THC (1-20 mg/kg), CBD (3-30 mg/kg), or sesame oil via oral gavage. Thermal and mechanical pain sensitivity (tail flick assay, von Frey test), rectal measurements for body temperature, locomotor activity, and the bar-test of catalepsy were completed. A separate group of rats (N=8/4 per sex) were administered morphine (5-20 mg/kg; intraperitoneal, IP) and evaluated for pain sensitivity as a positive control. Results We observed classic tetrad effects of antinociception, hypothermia, hyper- and hypolocomotion, and catalepsy after oral administration of THC that were long lasting (>7 hours). CBD modestly increased mechanical pain sensitivity and produced sex-dependent effects on body temperature and locomotor activity. Conclusions Oral THC and CBD produced long lasting effects, that differed in magnitude and time course when compared with other routes of administration. Examination of cannabinoid effects administered via different routes of administration, species, and in both males and females is critical to enhance translation.