bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential diagnosis and clinical management of isolated prolonged activated partial thromboplastin time in a patient with Hashimoto thyroiditis-associated thyroid cancer
Authors: Zhong Yuhong , Yan Biyong , Yu Zhongqi , Wang Lin
Published: July 2021

Rationale:

Patients preparing for surgery may have isolated, prolonged activated partial thromboplastin time (APTT). Cause analysis is warranted in patients who had neither bleeding symptom nor thromboembolic events because isolated prolongation of APTT may lead to unnecessary delayed surgical intervention or invasive procedure, even ineffective plasma infusion treatments. Here, we report a case of Hashimoto thyroiditis-associated thyroid cancer whose APTT was isolated prolonged and discuss the challenges of diagnosis and clinical management of this patient.

Patient concerns:

A 57-year-old woman was admitted to the hospital due to thyroid cancer. Anticoagulant assay was performed for this patient before surgery, she had normal values for prothrombin time, thrombin time, and fibrinogen, but had isolated prolonged APTT value (20 seconds longer than normal). However, the routine laboratory of the local hospital showed normal APTT and she did not have any abnormal bleeding or thrombotic episodes. Lupus anticoagulant (LA) was strongly positive according to mixing studies and modified dilute Russell viper venom time method, it was responsible for prolonged APTT.

Diagnoses:

Hashimoto thyroiditis-associated thyroid cancer whose APTT was isolated prolonged.

Interventions:

The isolated prolongation of APTT in this patient was due to LA. She had no history of anticoagulant medications and no spontaneous bleeding episodes. There should be no specific intervention before thyroidectomy.

Outcomes:

This thyroid cancer patient had an uneventful surgery and was discharged after a week.

Lessons:

Prolonged APTT is not considered an absolute indication for plasma infusion therapy in patients with LA. The correct identification of the cause of APTT prolongation is essential for proper treatment of the individuals.
Who's Getting Shots First? Dealing With the Ethical Responsibility for Prioritizing Population Groups in Vaccination
Authors: Rogozea Liliana M. , Sechel Gabriela , Bularca Maria C. , Coman Claudiu , Cocuz Maria E.
Published: July 2021

Background:

The current pandemic has raised several ethical dilemmas, related to conducting real-time trials for new treatments or vaccines or with decisions such as accessibility to vaccines.

Study Question:

Should there be a prioritization of access to the vaccine based on ethical and objective criteria or should the access be done at random?

Study Design:

To determine the ethics and reality of rationing the accessibility to anti-COVID vaccine according to the official strategies.

Data Sources:

The study is based on the consultation of (1) scientific articles from international databases (Google Scholar, PubMed, ProQuest, and Clarivate), (2) public health documents, and (3) official information of various governments.

Results:

The analyzed documents revealed that a few similarities can be observed in European countries when it comes to the first categories of people who have received the vaccine: people living in care facilities and medical staff; it can also be seen that the vaccination plan was adopted by each country for the needs and characteristics of its population, the prioritization being done in 2–14 stages; some of them divided, in their turn, into subsequent substages. Most of the states subject to the analysis assigned the medical staff in the first stage, followed by those in the sectors ensuring the maintenance of essential services, afterward by the elderly or people with comorbidities, only later to expand to other social categories.

Conclusions:

Prioritization of vaccine administration is not only necessary, unavoidable, but also problematic both ethically and logistically, which should involve leaders in the field of public health, but also medical staff, regardless of their specialization. Prioritization of vaccination can not only have an impact on individual health (physical and emotional) but also on society from public health, economic, and sociocultural point of view.
Pharmacological Management of Diabetes Mellitus: A Century of Expert Opinions in Cecil Textbook of Medicine
Authors: Manu Peter , Rogozea Liliana M. , Cernea Simona
Published: July 2021

Background:

Drug therapy for diabetes mellitus (DM) has had a significant impact on quality of life and work potential of affected persons and has contributed to a remarkable decrease in the frequency and severity of complications, hospitalizations, and mortality. The current approach is the result of incremental progress in using technological advances to increase the safety and effectiveness of insulin therapy and the introduction of new molecules as oral and injectable antidiabetic drugs.

Study Question:

What are the milestones of the changes in the expert approach to the pharmacological management of DM in the past century?

Study Design:

To determine the changes in the experts' approach to the management of DM, as presented in a widely used textbook in the United States.

Data Sources:

The chapters on describing the management of DM in the 26 editions of Cecil Textbook of Medicine published from 1927 to 2020.

Results:

In 1927, DM was treated with insulin extracted from the pancreas of large animals (cattle, hogs, and sheep) and purified with alcohol to prevent the tissues' proteolytic action on the hormone. The therapeutic milestones in DM marked 2 avenues for innovation. The first created advances in insulin therapy, starting with processes that led to the production of crystalline insulin and protamine zinc insulin (1937), synthetic human insulin (1996), and prandial (2000) and basal (2004) insulin analogues. The second was an effort to develop and introduce in clinical practice in the United States oral antidiabetic drugs, starting with tolbutamide, a sulfonylurea (1955), followed by metformin, a biguanide (1996), thiazolidinediones, alpha-glucosidase inhibitors, and benzoic acid derivatives (2000), dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists (2008), and sodium glucose cotransporter 2 inhibitors (2020). A latent period of 40 years between significant advances was likely because of searches for new technologies (eg, recombinant DNA for the production of synthetic insulin and analogues) and, at least in part, to the impact of the controversial University Group Diabetes Project on the development and acceptance of oral antidiabetic drugs.

Conclusions:

The pharmacological management of DM has progressed unevenly, with a long latency period in the second half of the last century followed by highly encouraging advances in the first 2 decades of the 21st century. In chronological order, the major advances were synthetic insulins obtained through DNA recombinant technology, adoption of metformin as first line therapy, and introduction of antidiabetic medication classes that also promote weight reduction and cardiovascular health.
Minimally invasive surgery for benign prostatic obstruction: new insights and future technical standards
Authors: Rijo Enrique , Hindley Richard , Tabatabaei Shahin , Bach Thorsten
Published: July 2021

Purpose of review

This review aims to give a brief description of the latest minimally invasive surgical techniques (MISTs) for the treatment of benign prostatic obstruction (BPO).

Recent findings

In recent years technological advances have made the implementation of MISTs in the armamentarium of BPO surgery possible and in many cases could replace standard procedures.

These techniques offer many advantages –short recovery time, rapid symptomatic relief, few adverse effects, lower risk of sexual/ejaculatory dysfunction, acceptable durability and most can be performed as an outpatient procedure.

Many of the newer MISTs can be performed outside the operating room under local anesthesia, hence the term office-based MIST.

A tailored BPO surgical treatment should not only take into account the prostate volume, but also many other factors including possible adverse events and the patient's expectations.

Further studies and long-term data are necessary to standardize methods for evaluating the outcomes of these new procedures and to see which will pass the test of time and end-up replacing the gold standard procedures.
Lymphoma in HIV-2-infected patients in combination antiretroviral therapy era
Authors: Ronchetti Anne-Marie , Matheron Sophie , Galicier Lionel , Damond Florence , Mahjoub Nadia , Chaghil Nathalie , Meignin Véronique , Mechaï Frédéric , Simon François , Oksenhendler Eric , Gérard Laurence
Published: July 2021

Objective:

To describe lymphoma in HIV-2-infected patients and compare their characteristics with lymphoma in HIV-1-infected patients.

Design:

Ancillary analysis from a single center prospective cohort of HIV-lymphoma.

Methods:

We report on 16 patients with HIV-2-lymphoma diagnosed after 1996 and included in a prospective cohort of HIV lymphoma. Five additional HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I (6 lymphomas) are separately reported. The incidence of lymphoma in HIV-2-infected patients was evaluated in the French multicentric HIV-2 cohort.

Results:

Incidence of lymphoma in the French HIV-2 cohort was estimated as 0.6/1000 patient-years. In our series, the median CD4+ cell count was 166 × 106/l at the time of lymphoma diagnosis and 50% of patients had undetectable plasma HIV-2-RNA. Lymphomas were non-Hodgkin lymphoma (n = 12) and classical Hodgkin lymphoma (n = 4). Similarly to HIV-1-lymphoma, clinical presentation was aggressive in most cases. All but one patient received intensive chemotherapy. Complete remission was achieved in 13 cases and 1 patient relapsed. The overall survival was not statistically different from that observed in patients with HIV-1 lymphoma. The six additional lymphomas observed in five HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I presented with similar clinical presentation but worse prognosis.

Conclusion:

Despite the lower pathogenicity of HIV-2, the risk of developing lymphoma seems to be close to that observed in HIV-1 population with similar lymphoma characteristics. Compared with HIV-1, HIV-2-infected patients developed lymphoma later in their life but at a similar CD4+ cell count level.
Long-Term Functional Outcomes of Trauma Patients With Facial Injuries
Authors: McCarty Justin C. , Herrera-Escobar Juan P. , Gadkaree Shekhar K. , El Moheb Mohamad , Kaafarani Haytham M.A. , Velmahos George , Salim Ali , Nehra Deepika , Caterson Edward J.
Published: July 2021

Background:

Facial trauma can have long-lasting consequences on an individual's physical, mental, and social well-being. The authors sought to assess the long-term outcomes of patients with facial injuries.

Methods:

This is a prospective multicenter cohort study of patients with face abbreviated injury scores ≥1 within the Functional Outcomes and Recovery after Trauma Emergencies registry. The Functional Outcomes and Recovery after Trauma Emergencies registry collects patient-reported outcomes data for patients with moderate-severe trauma 6 to 12 months after injury. Outcomes variables included general and trauma-specific quality of life, functional limitations, screening for post-traumatic stress disorder, and postdischarge healthcare utilization.

Results:

A total of 188 patients with facial trauma were included: 69.1% had an isolated face and/or head injury and 30.9% had a face and/or head injuries as a part of polytrauma injury. After discharge, 11.7% of patients visited the emergency room, and 13.3% were re-admitted to the hospital. Additionally, 36% of patients suffered from functional limitations and 17% of patients developed post-traumatic stress disorder. A total of 34.3% patients reported that their injury scars bothered them, and 49.4% reported that their injuries were hard to deal with emotionally.

Conclusions:

Patients who sustain facial trauma suffer significant long-term health-related quality of life consequences stemming from their injuries.
Fluorescence and Ultrasound-guided Laparoscopic Resection of Caudate Lobe for Hepatocellular Carcinoma Located in the Retrocaval Portion
Authors: Santambrogio Roberto , D’Alessandro Valentina , Iacob Giulio , Zappa Marco A.
Published: July 2021

Background:

Contrast-enhanced intraoperative ultrasonography (CEIOUS) and indocyanine green fluorescence were interesting tool for the visualization of intrahepatic neoplastic nodules. The combinations of the 2 technologies could increase tumor detection and the radicality of resection, allowing the use of a pure laparoscopic approach.

Methods:

The patient was an 81-year-old man with a history of hypertension and treated hepatitis C infection, with a sustained serological response from 2018, previously undergoing laparotomic resection for hepatocellular carcinoma (HCC) in segment 8.

During his regular hepatological follow-up, a 25 mm nodule was detected in segment 1, in a retrocaval position. Considering clinical presentation, good liver function (Child A5—MELD 8) and imaging, pure laparoscopic resection of the caudate lobe was performed using fluorescence imaging and CEIOUS navigation guidance.

Results:

The operation last for 205 minutes. Blood loss was 100 mL and no blood transfusion was required. She resumed diet on the next day and was discharged 4 days after the operation. Histopathologic examination showed 27 mm HCC with a clear margin. Contrast computed tomography scan performed 3 months after the operation showed no recurrence of the disease.

Conclusions:

A laparoscopic isolated caudate resection for HCC located in the retrocaval portion of the cirrhotic liver seems to be feasible in selected patients and fluorescence imaging and CEIOUS navigation guidance could guarantee a safe and successful surgery.
Unequal distribution of financial toxicity among people with cancer and its impact on access to care: a rapid review
Authors: Longo Christopher J. , Fitch Margaret I.
Published: July 2021

Purpose of review

Research demonstrates that patients and their families often carry a good portion of the economic burden during and following cancer treatment, frequently resulting in implications for access to care. This rapid review summarizes how this knowledge has evolved in recent years.

Recent findings

The number of articles on patient financial burden is increasing, suggesting awareness about the growing impact of economic burden on patients. This is particularly evident when discussing out-of-pocket costs, and lost work for patients/caregivers. However, there is an increasing focus on ‘foregone care’ and ‘financial distress’. Additionally, emerging literature is examining policies and approaches to screen and/or mitigate these patient financial risks, thereby improving access to care. There is also increasing focus on populations that shoulder a disproportionate financial burden, including ethnic minorities (blacks, Asians, Latinos) as well as those with lower socioeconomic status. Additionally, there is evidence that this burden also affects the middle class.

As healthcare budgets become stretched, especially during a pandemic, supportive programs benefiting the less fortunate often shrink, which impacts access to care. The emerging research on strategies with government or institutions to mitigate these burdens and access issues are both welcome and needed.
Degraded pastures in Brazil: improving livestock production and forest restoration
Authors: Feltran-Barbieri Rafael , Féres José Gustavo
Published: July 2021

Degraded pasture is a major liability in Brazilian agriculture, but restoration and recovery efforts could turn this area into a new frontier to both agricultural yield expansion and forest restoration. Currently, rural properties with larger degraded pasture areas are associated with higher levels of technical inefficiency in Brazil. The recovery of 12 million ha of degraded pastures could generate an additional production of 17.7 million bovines while reducing the need for new agricultural land. Regional identification of degraded pastures would facilitate the targeting of agricultural extension and advisory services and rural credit efforts aimed at fostering pasture recovery. Since only 1% of Brazilian municipalities contain 25% of degraded pastures, focusing pasture recovery efforts on this small group of municipalities could generate considerable benefits. More efficient allocation of degraded and native pastures for meat production and forest restoration could provide land enough to fully comply with its Forest Code requirements, while adding 9 million heads to the cattle inventory. Degraded pasture recovery and restoration is a win–win strategy that could boost livestock husbandry and avoid deforestation in Brazil and has to be the priority strategy of agribusiness sector.
Quantifying the preventive effect of wearing face masks
Authors: Britton Tom
Published: July 2021

An important task in combating the current Covid-19 pandemic lies in estimating the effect of different preventive measures. Here, we focus on the preventive effect of enforcing the use of face masks. Several publications study this effect, however, often using different measures such as: the relative attack rate in case-control studies, the effect on incidence growth/decline in a specific time frame and the effect on the number of infected in a given time frame. These measures all depend on community-specific features and are hence not easily transferred to other community settings. We argue that a more universal measure is the relative reduction in the reproduction number, which we call the
face mask effect
,
E
FM
. It is shown how to convert the other measures to
E
FM
. We also apply the methodology to four empirical studies using different effect-measures. When converted to estimates of
E
FM
, all estimates lie between 15 and 40%, suggesting that mandatory face masks reduce the reproduction number by an amount in this range, when compared with no individuals wearing face masks.
Imitation and aspiration dynamics bring different evolutionary outcomes in feedback-evolving games
Authors: Arefin Md. Rajib , Tanimoto Jun
Published: July 2021

Feedback-evolving games characterize the interplay between the evolution of strategies and environments. Rich dynamics have been derived for such games under the premise of the replicator equation, which unveils persistent oscillations between cooperation and defection. Besides replicator dynamics, here we have employed aspiration dynamics, in which individuals, instead of comparing payoffs with opposite strategies, assess their payoffs by self-evaluation to update strategies. We start with a brief review of feedback-evolving games with replicator dynamics and then comprehensively discuss such games with aspiration dynamics. Interestingly, the tenacious cycles, as perceived in replicator dynamics, cannot be observed in aspiration dynamics. Our analysis reveals that a parameter
θ
—which depicts the strength of cooperation in enhancing the environment—plays a pivotal role in comprehending the dynamics. In particular, with the symmetric aspiration level, if replete and depleted states, respectively, experience Prisoner's Dilemma and Trivial games, the rich environment is achievable only when
θ
 > 1. The case
θ
 < 1 never allows us to reach the replete state, even with a higher cooperation level. Furthermore, if cooperators aspire less than defectors, then the enhanced state can be achieved with a relatively lower
θ
value compared with the opposite scenario because too much expectation from cooperation can be less beneficial.
Palaeoproteomic analyses of dog palaeofaeces reveal a preserved dietary and host digestive proteome
Authors: Runge Anne Kathrine W. , Hendy Jessica , Richter Kristine K. , Masson-MacLean Edouard , Britton Kate , Mackie Meaghan , McGrath Krista , Collins Matthew , Cappellini Enrico , Speller Camilla
Published: July 2021

The domestic dog has inhabited the anthropogenic niche for at least 15 000 years, but despite their impact on human strategies, the lives of dogs and their interactions with humans have only recently become a subject of interest to archaeologists. In the Arctic, dogs rely exclusively on humans for food during the winter, and while stable isotope analyses have revealed dietary similarities at some sites, deciphering the details of provisioning strategies have been challenging. In this study, we apply zooarchaeology by mass spectrometry (ZooMS) and liquid chromatography tandem mass spectrometry to dog palaeofaeces to investigate protein preservation in this highly degradable material and obtain information about the diet of domestic dogs at the Nunalleq site, Alaska. We identify a suite of digestive and metabolic proteins from the host species, demonstrating the utility of this material as a novel and viable substrate for the recovery of gastrointestinal proteomes. The recovered proteins revealed that the Nunalleq dogs consumed a range of Pacific salmon species (coho, chum, chinook and sockeye) and that the consumed tissues derived from muscle and bone tissues as well as roe and guts. Overall, the study demonstrated the viability of permafrost-preserved palaeofaeces as a unique source of host and dietary proteomes.
Chryseobacterium caseinilyticum sp. nov., a casein hydrolyzing bacterium isolated from rice plant and emended description of Chryseobacterium piscicola
Authors: Chhetri Geeta , Kim Jiyoun , Kim Inhyup , Kang Minchung , Seo Taegun
Published: July 2021

A novel Gram-stain-negative, aerobic, asporogenous, catalase-positive and oxidase-negative, non-motile, golden-yellow pigmented, rod-shaped bacterium with casein-degrading ability, designated strain GCR10T, was isolated from roots of rice plants collected from a paddy field near Dongguk University, Republic of Korea. The results of subsequent 16S rRNA gene sequence analysis indicated that GCR10T shares the highest sequence identity with

Chryseobacterium piscicola

VQ-6316sT (98.3%). Strain GCR10T grew at 2–32 °C (optimum, 25 °C), at pH 6.0–8.0 (optimum, pH 7.0) and in the presence of 0–2.0% (w/v) NaCl (optimum in the absence of NaCl). The novel strain was able to produce carotenoid and flexirubin-type pigments. The predominant menaquinone was MK-6 and the major fatty acids were identified as iso-C15 : 0, iso-C17 : 0 3-OH and iso-C17 : 1ω9c. The polar lipids were phosphatidylethanolamine, four unidentified aminoglycolipids, two unidentified aminolipids and two unidentified glycolipids. The genome of GCR10T is 4.3 Mb in length with a DNA G+C content of 36.5 mol%. Average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity values between GCR10T and

Chryseobacterium piscicola

VQ-6316sT were 82.1, 25.2 and 84.3 %, respectively, which clearly indicates that the novel strain is distinct from its closest relative. The demand for natural biodegradable pigments isolated frominsects, plants or microorganisms is increasing day by day because of their beneficial pharmacological properties. Here, we describe a novel strain that produces two types of pigment, carotenoid and flexirubin. On the basis of the results from phenotypic, genotypic and chemotaxonomic analyses, strain GCR10T represents a novel species of the genus

Chryseobacterium

, and the name Chryseobacterium caseinilyticum sp. nov. is proposed. The type strain is GCR10T (=KACC 21707T=NBRC 114715T).
Strategy and performance evaluation of low-frequency variant calling for SARS-CoV-2 in wastewater using targeted deep Illumina sequencing
Authors: Van Poelvoorde Laura A. E. , Delcourt Thomas , Coucke Wim , Herman Philippe , De Keersmaecker Sigrid C. J. , Saelens Xavier , Roosens Nancy , Vanneste Kevin
Published: July 2021

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, constitutes a tremendous global health issue. Continuous monitoring of the virus has become a cornerstone to make rational decisions on implementing societal and sanitary measures to curtail the virus spread. Additionally, emerging SARS-CoV-2 variants have increased the need for genomic surveillance to detect particular strains because of their potentially increased transmissibility, pathogenicity and immune escape. Targeted SARS-CoV-2 sequencing of wastewater has been explored as an epidemiological surveillance method for the competent authorities. Few quality criteria are however available when sequencing wastewater samples, and those available typically only pertain to constructing the consensus genome sequence. Multiple variants circulating in the population can however be simultaneously present in wastewater samples. The performance, including detection and quantification of low-abundant variants, of whole genome sequencing (WGS) of SARS-CoV-2 in wastewater samples remains largely unknown. Here, we evaluated the detection and quantification of mutations present at low abundances using the SARS-CoV-2 lineage B.1.1.7 (alpha variant) defining mutations as a case study. Real sequencing data were in silico modified by introducing mutations of interest into raw wild-type sequencing data, or by mixing wild-type and mutant raw sequencing data, to mimic wastewater samples subjected to WGS using a tiling amplicon-based targeted metagenomics approach and Illumina sequencing. As anticipated, higher variation, lower sensitivity and more false negatives, were observed at lower coverages and allelic frequencies. We found that detection of all low-frequency variants at an abundance of 10%, 5%, 3% and 1%, requires at least a sequencing coverage of 250X, 500X, 1500X and 10,000X, respectively. Although increasing variability of estimated allelic frequencies at decreasing coverages and lower allelic frequencies was observed, its impact on reliable quantification was limited. This study provides a highly sensitive low-frequency variant detection approach, which is publicly available at https://galaxy.sciensano.be, and specific recommendations for minimum sequencing coverages to detect clade-defining mutations at specific allelic frequencies.
Entering into a self-regulated learning mode prevents detrimental effect of feedback removal on memory
Authors: Vavra Peter , Sokolovič Leo , Porcu Emanuele , Ripollés Pablo , Rodriguez-Fornells Antoni , Noesselt Toemme
Published: July 2021

Recently, we provided causal evidence that self-regulated dopamine signaling enhanced long-term memory formation in the absence of any external feedback or reward (Ripollés et al., 2016, 2018) if a congruent meaning inferred from semantic context (DA-dependent learning), while DA-signals were absent if no congruent meaning could be inferred (DA-independent learning). Here, we investigated the interaction of self-regulated learning with externally-regulated DA-signalling by providing external performance feedback in the first or second half of trials. We found that removing feedback during DA-dependent learning lowered subsequent recognition rates a day later, whereas recognition remained high in the group which received feedback only in the second half. In contrast, feedback modestly enhanced recognition rates for both groups for DA-independent learning. Our findings suggest that external reinforcers can selectively impair DA-dependent memories if internal DA-dependent processes are not already established and highlights the relevance of self-regulated learning in education to support stable memory formation.
Phylogenomics, Epigenomics, Virulome, and Mobilome of Gram-negative Bacteria Co-resistant to Carbapenems and Polymyxins: A One-Health Systematic Review and Meta-analyses
Authors: Ramaloko Winnie Thabisa , Sekyere John Osei
Published: July 2021

Gram-negative bacteria (GNB) continue to develop resistance against important antibiotics including last-resort ones such as carbapenems and polymyxins. An analysis of GNB with co-resistance to carbapenems and polymyxins from a One Health perspective is presented.

Data of species name, country, source of isolation, resistance genes (ARGs), plasmid type, clones, and mobile genetic elements (MGEs) were deduced from 129 articles from January 2016 to March 2021. Available genomes and plasmids were obtained from PATRIC and NCBI. Resistomes and methylomes were analysed using BAcWGSTdb and REBASE whilst Kaptive was used to predict capsule typing. Plasmids and other MEGs were identified using MGE Finder and ResFinder. Phylogenetic analyses were done using RAxML and annotated with MEGA 7.

A total of 877 isolates, 32 genomes and 44 plasmid sequences were analysed. Most of these isolates were reported in Asian countries and were isolated from clinical, animal, and environmental sources. Colistin resistance was mostly mediated by mgrB inactivation, while OXA-48/181 was the most reported carbapenemase. IncX and IncI were the most common plasmids hosting carbapenemases and mcr genes. The isolates were co-resistant to other antibiotics, with floR (chloramphenicol) and fosA3 (fosfomycin) being common; E. coli ST156 and K. pneumoniae ST258 strains were common globally. Virulence genes and capsular KL-types were also detected. Type I, II, III and IV restriction modification systems were detected, comprising various MTases and restriction enzymes. The escalation of highly resistant isolates drains the economy due to untreatable bacterial infections, which leads to increasing global mortality rates and healthcare costs.

Author summary

Carbapenem and polymyxin co-resistance in Gram-negative bacteria (GNB) is a growing public health concern globally. China presented a high number of highly resistant bacteria from humans, animals, and environmental samples. Escherichia coli isolates were the most dominant in China, while Klebsiella pneumoniae isolates dominated Greece, the second country with high numbers of carbapenem and colistin co-resistant strains. Mobile genetic elements including plasmids are responsible for disseminating such resistance genes. Worryingly, GNB with Carbapenem and polymyxin co-resistance also harbours genes that make them resistant to other antibiotics, making them multi-drug resistant.
Peritraumatic Distress of COVID-19 on Physicians in Bangladesh: Implications and Policy Recommendations
Authors: Ahmad Zafar , Kium Abdullah al , Ahammed Md Ripon , Hamid Md Montaser , Tarannum Sarmina , Amin Md. Ruhul , Islam Md. Daharul
Published: July 2021

COVID-19 pandemic has been an ultimate test of resource management for any governance, especially in the healthcare system. Bangladesh, being a developing country and with very limited resources, is fighting the COVID-19 pandemic. The frontline workers, especially the physicians and nurses are going through immense physical and psychological stress during the pandemic. Social unawareness, the absence of strict preventive policies, increasing workload, and the lack of resource management are making the frontline healthcare workers extremely vulnerable to COVID-19. In this paper, we present the outcome of our study on peritraumatic distress of COVID-19 among physicians in Bangladesh. Based on the user study, we have identified a number of key factors behind the peritraumatic distress and psychological stress caused by COVID-19. Our study shows, more than 78% respondents are suffering from peritraumatic psychological distress. We also recommended some very important and yet easy to implement policies to reduce the peritraumatic stress of the physicians of Bangladesh. These policy recommendations were a result of the survey analysis and the suggestions from the COVID-19 designated physicians.
Mouse Antibodies with Activity Against the SARS-CoV-2 D614G and B.1.351 Variants
Authors: Troitskaya Larisa , Shun Chan Nelson Lap , Frank Brendon , Capon Daniel J. , Zabel Brian A. , Ge Xiaomei , Luo Dan , Martinelli Rachel , Jin Jing , Simmons Graham
Published: July 2021

With the rapid spread of SARS-CoV-2 variants, including those that are resistant to antibodies authorized for emergency use, it is apparent that new antibodies may be needed to effectively protect patients against more severe disease. Differences between the murine and human antibody repertoires may allow for the isolation of murine monoclonal antibodies that recognize a different or broader range of SARS-CoV-2 variants than the human antibodies that have been characterized so far. We describe mouse antibodies B13 and O24 that demonstrate neutralizing potency against SARS-CoV-2 Wuhan (D614G) and B.1.351 variants. Such murine antibodies may have advantages in protecting against severe symptoms when individuals are exposed to new SARS-CoV-2 variants.
Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine
Authors: Kardava Lela , Rachmaninoff Nicholas , Lau William W. , Buckner Clarisa M. , Trihemasava Krittin , de Assis Felipe Lopes , Wang Wei , Zhang Xiaozhen , Wang Yimeng , Chiang Chi-I , Narpala Sandeep , Reger Robert , McCormack Genevieve E. , Seamon Catherine A. , Childs Richard W. , Suffredini Anthony F. , Strich Jeffrey R. , Chertow Daniel S. , Davey Richard T. , Sneller Michael C. , O’Connell Sarah , Li Yuxing , McDermott Adrian , Chun Tae-Wook , Fauci Anthony S. , Tsang John S. , Moir Susan
Published: July 2021

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.
Characteristics of children and antigen test performance at a SARS-CoV-2 community testing site
Authors: Ford Laura , Whaley Melissa J. , Shah Melisa M. , Salvatore Phillip P. , Segaloff Hannah E. , Delaney Augustina , Currie Dustin W. , Boyle-Estheimer Lauren , O’Hegarty Michelle , Morgan Clint N. , Meece Jennifer , Ivacic Lynn , Thornburg Natalie J. , Tamin Azaibi , Harcourt Jennifer L. , Folster Jennifer M. , Medrzycki Magdalena , Jain Shilpi , Wong Phili , Goffard Kimberly , Gieryn Douglas , Kahrs Juliana , Langolf Kimberly , Zochert Tara , Tate Jacqueline E. , Hsu Christopher H. , Kirking Hannah L.
Published: July 2021

Background

Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture.

Methods

Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults.

Results

About one in ten included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR positive. Cycle threshold values were similar among RT-PCR positive specimens from children and adults (22.5 vs 21.3, p=0.46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, p=0.39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive value were 100% (27/27) and 94.9% (188/198) respectively. Virus was isolated from 51.4% (19/37) of RT-PCR positive pediatric specimens; all 19 had positive antigen test results.

Conclusions

With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.
Characterization of the Drosophila adult hematopoietic system reveals a rare cell population with differentiation and proliferation potential
Authors: Boulet Manon , Renaud Yoan , Lapraz François , Benmimoun Billel , Vandel Laurence , Waltzer Lucas
Published: July 2021

While many studies have described Drosophila embryonic and larval blood cells, the hematopoietic system of the imago remains poorly characterized and conflicting data have been published concerning adult hematopoiesis. Using a combination of blood cell markers, we show that the adult hematopoietic system is essentially composed of a few distinct mature blood cell types. In addition, our transcriptomics results indicate that adult and larval blood cells have both common and specific features and it appears that adult hemocytes reactivate many gene expressed in embryonic blood cells. Interestingly, we identify a small set of blood cells that do not express differentiation markers but maintain the progenitor markerdomeMeso. Yet, we show that these cells are derived from the posterior signaling center, a specialized population of cells present in the larval lymph gland, rather than from larval blood cell progenitors, and that their maintenance depends on the EBF transcription factor Collier. Furthermore, while these cells are normally quiescent, we find that some of them can differentiate and proliferate in response to bacterial infection. In sum, our results indicate that adult flies harbor a small population of specialized cells with limited hematopoietic potential and further support the idea that no substantial hematopoiesis takes place during adulthood.
Human Papillomavirus Type 16 E6 induces cell competition
Authors: Brimer Nicole , Pol Scott Vande
Published: July 2021

High risk human papillomavirus (HPV) infections induce squamous epithelial tumors in which the virus replicates. Initially, the virus-infected epithelial cells are untransformed, but expand in both number and area at the expense of normal squamous epithelial cells. How this occurs is unknown, but is presumed to be due to viral oncogene expression. We have developed an in vitro assay in which colonies of post-confluent HPV16 expressing cells outcompete confluent surrounding normal keratinocytes for surface area. The enhanced cell competition induced by the complete HPV16 genome is conferred by E6 expression alone, and not by individual expression of E5 or E7. In traditional oncogene assays, E7 is a more potent oncogene than E6, but such assays do not include interaction with normal surrounding cells. These new results separate classic oncogenicity that is primarily conferred by E7, from cell competition that we show is primarily conferred by E6, and provides a new biological role for E6 oncoproteins from high risk human papillomaviruses.

Importance

High risk papillomavirus infections induce epithelial tumors, some of which evolve into malignancies. The development and maintenance of cancer is due to the virally encoded E6 and E7 oncoproteins. How a virally infected keratinocyte out-competes normal uninfected keratinocytes has been unknown. The present work shows that the enhanced competition of HPV16-infected cells is primarily due to the expression of the E6 oncoprotein and not the E7 or E5 oncoproteins. This work shows the importance of measuring oncoprotein traits in the context of cell competition with uninfected cells, and shows the potential of papillomavirus oncoproteins to be novel genetic probes for the analysis of cell competition.
The orexigenic force of olfactory palatable food cues in sated rats
Authors: Peris-Sampedro Fiona , Stoltenborg Iris , Le May Marie V. , Solé-Navais Pol , Adan Roger A. H. , Dickson Suzanne L.
Published: July 2021

Background

Environmental cues recalling palatable foods are ubiquitous and motivate eating beyond metabolic need, yet the timing of this response and whether it can develop towards a non-palatable readily available food remain elusive. Although there is increasing evidence indicating that external stimuli in the olfactory modality can communicate with the major hub in the feeding neurocircuitry, the hypothalamic arcuate nucleus (Arc), the identity of hypothalamic substrates has been only partially uncovered.

Methods

Using a palatable home-cage hidden-food paradigm, we investigate the ability of olfactory food cues to promote chow overconsumption in sated male rats, together with their impact on meal pattern. We likewise explore, by means of an immediate early gene marker, the neural mechanisms involved, including the possible engagement of the orexigenic ghrelin system.

Results

Olfactory detection of a familiar palatable food shifts diurnal patterns towards an increase in meal frequency to cause persistent overconsumption of chow in sated conditions. In line with the orexigenic response observed, sensing the palatable food in the environment stimulates food-seeking and risk-taking behavior, and also triggers release of active ghrelin. Olfactory food cues recruit intermingled populations of cells embedded within the feeding circuitry within the Arc, including, notably, those containing the ghrelin receptor, even when food is not available for consumption.

Conclusions

These data demonstrate leverage of ubiquitous food cues, not only for palatable food-searching, but also to powerfully drive food consumption in ways that resonate with heightened hunger, for which the orexigenic ghrelin system is implicated.
Development of Kaptive databases for Vibrio parahaemolyticus O- and K-antigen serotyping
Authors: van der Graaf – van Bloois Linda , Chen Hongyou , Wagenaar Jaap A. , Zomer Aldert L.
Published: July 2021

Vibrio parahaemolyticus is an important food-borne human pathogen and is divided in 16 O- serotypes and 71 K-serotypes. Agglutination tests are still the gold standard for serotyping, but many V. parahaemolyticus isolates are not typable by agglutination. An alternative for agglutination tests is serotyping using whole genome sequencing data. In this study, V. parahaemolyticus isolates are serotyped and sequenced, and all known and several novel O- and K-loci are identified. We developed Kaptive databases for all O- and K-loci after manual curation of the loci. These Kaptive databases with the identified V. parahaemolyticus O- and K -loci can be used to identify the O- and K-serotypes of V. parahaemolyticus isolates from genome sequences.
Breast invasive ductal carcinoma classification on whole slide images with weakly-supervised and transfer learning
Authors: Kanavati Fahdi , Tsuneki Masayuki
Published: July 2021

Abstract

Invasive ductal carcinoma (IDC) is the most common form of breast cancer. For the non-operative diagnosis of breast carcinoma, core needle biopsy has been widely used in recent years which allows evaluation of both cytologic and tissue architectural features; so that it can provide a definitive diagnosis between IDC and benign lesion (e.g., fibroadenoma). Histopathological diagnosis based on core needle biopsy specimens is currently the cost effective method; therefore, it is an area that could benefit from AI-based tools to aid pathologists in their pathological diagnosis workflows. In this paper, we trained an Invasive Ductal Carcinoma (IDC) Whole Slide Image (WSI) classification model using transfer learning and weakly-supervised learning. We evaluated the model on a core needle biopsy (n=522) test set as well as three surgical test sets (n=1129) obtaining ROC AUCs in the range of 0.95-0.98.
LI-Seq: A Cost-Effective, Low Input DNA method for Whole Genome Library Preparation
Authors: Schweizer Teia M. , DeSaix Matthew G. , Ruegg Kristen C.
Published: July 2021

Samples from species of high conservation concern are often low in total genomic DNA. Whole Genome Sequencing (WGS) can provide many insights that can be used to aid in species conservation, but current methods for working with low quality and low input samples can be cost prohibitive for population level genomic analyses. Thus, there is an urgent need for a cost-effective method of preparing WGS libraries from low input DNA samples.

To bridge the gap between sampling techniques commonly used in conservation genetics that yield low quality and low input DNA and the powerful tool of WGS, we developed LI-Seq, a more efficient method that successfully produces libraries from low quality DNA with as low input as 0.48 ng of DNA, with an average final library size of 300-500 base pairs.

Sequencing results suggest no difference in sequencing quality or coverage between low quality, low input and high quality, high input starting material using our protocol. We conclude that our new method will facilitate high-throughput WGS on low quality, low input samples, thus expanding the power of genomic tools beyond traditional high quality samples.
Predictability and parallelism in the contemporary evolution of hybrid genomes
Authors: Langdon Quinn K. , Powell Daniel L. , Kim Bernard , Banerjee Shreya M. , Payne Cheyenne , Dodge Tristram O. , Moran Ben , Fascinetto-Zago Paola , Schumer Molly
Published: July 2021

Hybridization between species is widespread across the tree of life. As a result, many species, including our own, harbor regions of their genome derived from hybridization. Despite the recognition that this process is widespread, we understand little about how the genome stabilizes following hybridization, and whether the mechanisms driving this stabilization tend to be shared across species. Here, we dissect the drivers of variation in local ancestry across the genome in replicated hybridization events between two species pairs of swordtail fish: Xiphophorus birchmanni × X. cortezi and X. birchmanni × X. malinche. We find unexpectedly high levels of repeatability in local ancestry across the two types of hybrid populations. This repeatability is attributable in part to the fact that the recombination landscape and locations of functionally important elements play a major role in driving variation in local ancestry in both types of hybrid populations. Beyond these broad scale patterns, we identify dozens of regions of the genome where minor parent ancestry is unusually low or high across species pairs. Analysis of these regions points to shared sites under selection across species pairs, and in some cases, shared mechanisms of selection. We show that one such region is a previously unknown hybrid incompatibility that is shared across X. birchmanni × X. cortezi and X. birchmanni × X. malinche hybrid populations.