bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deeply functional identification of TCS1 alleles provides efficient technical paths for low-caffeine breeding of tea plants
Authors: Wang Yi , Liu Yu-Fei , Wei Meng-Yuan , Zhang Chen-Yu , Chen Jie-Dan , Yao Ming-Zhe , Chen Liang , Jin Ji-Qiang 
Published: December 2022

Abstract
Caffeine is an important functional component in tea, which has the effect of excitement and nerve stimulation, but excessive intake can cause insomnia and dysphoria. Therefore, the production of tea with low-caffeine content can meet the consumption needs of certain people. Here, in addition to the previous alleles of the tea caffeine synthase (TCS1) gene, a new allele (TCS1h) from tea germplasms was identified. Results of in vitro activity analysis showed that TCS1h had both theobromine synthase (TS) and caffeine synthase (CS) activities. Site-directed mutagenesis experiments of TCS1a, TCS1c, and TCS1h demonstrated that apart from the 225th amino acid residue, the 269th amino acid also determined the CS activity. GUS histochemical analysis and dual-luciferase assay indicated the low promoter activity of TCS1e and TCS1f. In parallel, insertion and deletion mutations in large fragments of alleles and experiments of site-directed mutagenesis identified a key cis-acting element (G-box). Furthermore, it was found that the contents of purine alkaloids were related to the expression of corresponding functional genes and alleles, and the absence or presence and level of gene expression determined the content of purine alkaloids in tea plants to a certain extent. In summary, we concluded TCS1 alleles into three types with different functions and proposed a strategy to effectively enhance low-caffeine tea germplasms in breeding practices. This research provided an applicable technical avenue for accelerating the cultivation of specific low-caffeine tea plants.
A Blue Future: developing a national marine litter action plan in SIDS—lessons learnt in Belize
Authors: Monsanto Maxine , Kohler Peter , Binetti Umberto , Silburn Briony , Russell Josie , Corbin Chris , Lyons Brett , Birchenough Silvana N R , Maes Thomas 
Published: December 2022

Abstract
Marine litter is a significant global threat. The complex and cross cutting nature involved in tackling marine litter requires a coordinated response involving multiple sectors and a broad range of stakeholders. Small Island Developing States (SIDS) are particularly vulnerable to detrimental impacts of marine litter on quality of life and economies, particularly tourism and fisheries sectors. This paper presents national Marine Litter Action Plans (MLAP) as effective tools for coordinating responses addressing marine litter and specifically outlines the process undertaken to develop a national MLAP for the country of Belize, a Caribbean SIDS. Actions included in the MLAP, adopted by Belize in 2019, focused on developing science related to marine litter through monitoring and capacity building, tackling land- and sea-based sources through enforcement and planning, and boosting awareness through outreach and education. The paper further summarizes common challenges faced by SIDS and identifies key enabling conditions that facilitated MLAP development and adoption from perspective of a Caribbean SIDS. These experiences from Belize include stakeholder engagement, communication, governance, transparency, equity, scientific surveys, data gaps, and capacity building. The lessons learned from this practical application can be applied when developing and implementing MLAPs in other SIDS and beyond.
Economic evaluation of antimicrobial use practices in animal agriculture: a case of poultry farming
Authors: Lhermie Guillaume , Ndiaye Youba , Rushton Jonathan , Raboisson Didier 
Published: December 2022

Abstract

Background
The growing evidence of the contribution of antimicrobial use (AMU) in animal agriculture to the public health threat of antimicrobial resistance has highlighted to policymakers the importance of the need for prudent AMU in animal production. Livestock farming is an economic process, where farmers are using inputs such as antimicrobials to minimize their losses.

Objectives
Using a large and unique dataset combining time-series data on economic performance and health records in conventional broiler production in France, we identify how improved healthcare management and disease prevention impact economic performance, AMU reduction and health outcomes.

Methods
We analyse the main characteristics of the economic performance of farms measured by the profit per m2, by performing advanced regression models investigating the relative importance of medication and veterinary procedures.

Results
In our study, 50% of the treatments (expressed as number of new treatments) are attributable to only 30% of all flocks. There is an inverted U-shaped relationship between AMU and economic performance. This finding implies that the marginal profit of antimicrobials is decreasing, meaning that using antimicrobials is only profitable up to a certain threshold. Results also show that the profit increases as the number of preventive treatments increase.

Conclusions
Our findings suggest that policies encouraging farmers to work upstream from the occurrence of disease have the potential to perform better than regulations, as they would maintain a profitable activity while diminishing AMU. Encouraging adequate infection control practices by subsidizing or providing other incentives would benefit farmers and society.
Dalbavancin in clinical practice in Spain: a 2 year retrospective study
Authors: Morata Laura , Aguado José María , Salavert Miguel , Pasquau Juan , Míguez Enrique , Muñoz Patricia , Rosselló Irantzu , Almirante Benito 
Published: December 2022

Abstract

Objectives
Dalbavancin is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults. Its unique pharmacokinetic properties allow daily dosing to be avoided. The objective was to describe the sociodemographic and clinical characteristics of patients treated with dalbavancin in Spain, and to evaluate its effectiveness and safety in real-world settings.

Patients and methods
This non-interventional, retrospective, observational and multicentre study included patients who received at least one dose between 2018 and 2019 in seven Spanish hospitals.

Results
In total, 187 patients were included. The most common comorbidities were cardiovascular disease (27.4%) and diabetes mellitus (23.5%). Dalbavancin was used to treat osteoarticular infections (28.3%), ABSSSIs (22.5%), cardiovascular infections (20.9%) and catheter-related infections (18.2%). The most prevalent pathogens were Staphylococcus aureus (34.2%), CoNS (32.6%), and enterococci (12.8%). The main reason for use was early hospital discharge (65.8%). Most patients were treated with 1500 mg in a single dose (35.3%) and the median duration of treatment was 2 weeks. The treatment was clinically successful in 91.4% of cases. Six patients (3.2%) reported adverse events. Physicians agreed on the potential reduction of hospitalization days (85.3%). A subanalysis of patient characteristics and type of pathogen showed similar results in terms of efficacy and safety.

Conclusions
Dalbavancin seems to be effective and safe as second-line treatment in severe Gram-positive infections. It improves treatment adherence and allows outpatient management. Furthermore, the effectiveness and safety profile are maintained against diverse microorganisms in Gram-positive infections and regardless of the patients’ comorbidities at baseline, or age.
Prevalence and antimicrobial resistance patterns ofEnterococcusspecies isolated from laying hens in Lusaka and Copperbelt provinces of Zambia: a call for AMR surveillance in the poultry sector
Authors: Mudenda Steward , Matafwali Scott Kaba , Malama Sydney , Munyeme Musso , Yamba Kaunda , Katemangwe Patrick , Siluchali Godfrey , Mainda Geoffrey , Mukuma Mercy , Bumbangi Flavien Nsoni , Mirisho Robert , Muma John Bwalya 
Published: December 2022

AbstractBackgroundThe use of antimicrobials in layer poultry production for improved production, growth promotion, prophylaxis and treatment purposes has contributed to the development of antimicrobial resistance (AMR) in poultry. In Zambia, there is a paucity of information on the prevalence and AMR patterns of Enterococcus species isolated from laying hens.ObjectivesThis study investigated the prevalence and AMR patterns of enterococci isolated in layer hens in Lusaka and Copperbelt provinces of Zambia.MethodsA cross-sectional study was conducted from September 2020 to April 2021. Three hundred and sixty-five pooled cloacal swab samples were collected from 77 layer poultry farms. Enterococci identification and confirmation were performed using Analytical Profile Index (API 20 STREP) and 16S rRNA sequencing, respectively. A panel of nine antibiotics was used for antibiotic susceptibility testing and interpreted according to the CLSI 2020 guidelines. Data were analysed using SPSS version 23 and WHONET 2020.ResultsA total of 308 (84.4%) single Enterococcus species isolates were obtained and showed resistance to tetracycline (80.5%), erythromycin (53.6%), quinupristin/dalfopristin (53.2%), ampicillin (36.72%), vancomycin (32.8%), linezolid (30.2%), ciprofloxacin (11.0%), nitrofurantoin (6.5%) and chloramphenicol (3.9%). The prevalence of enterococci resistant to at least one antibiotic was 99.4% (n = 306), of which 86% (n = 265) were MDR.ConclusionsThis study found a high prevalence of antimicrobial-resistant enterococci. The presence of MDR requires urgent intervention and implementation of AMR surveillance strategies and antimicrobial stewardship programmes in layer poultry production in Zambia.
Clinical informatics training in medical school education curricula: a scoping review
Authors: Zainal Humairah , Tan Joshua Kuan , Xiaohui Xin , Thumboo Julian , Yong Fong Kok 
Published: December 2022

AbstractObjectivesThis scoping review evaluates the existing literature on clinical informatics (CI) training in medical schools. It aims to determine the essential components of a CI curriculum in medical schools, identify methods to evaluate the effectiveness of a CI-focused education, and understand its delivery modes.Materials and MethodsThis review was informed by the methodological guidance of the Joanna Briggs Institute. Three electronic databases including PubMed, Scopus, and Web of Science were searched for articles discussing CI between January 2010 and December 2021.ResultsFifty-nine out of 3055 articles were included in our final analysis. Components of CI education include its utilization in clinical practice, ethical implications, key CI-related concepts, and digital health. Evaluation of educational effectiveness entails external evaluation by organizations external to the teaching institute, and internal evaluation from within the teaching institute. Finally, modes of delivery include various pedagogical strategies and teaching CI using a multidisciplinary approach.DiscussionGiven the broad discussion on the required competencies, we propose 4 recommendations in CI delivery. These include situating CI curriculum within specific contexts, developing evidence-based guidelines for a robust CI education, developing validated assessment techniques to evaluate curriculum effectiveness, and equipping educators with relevant CI training.ConclusionThe literature reveals that CI training in the core curricula will complement if not enhance clinical skills, reiterating the need to equip students with relevant CI competencies. Furthermore, future research needs to comprehensively address current gaps in CI training in different contexts, evaluation methodologies, and delivery modes to facilitate structured training.
WIPO’s Contributions to International Cooperation on Intellectual Property
Authors: Jorgenson Lisa , Fink Carsten 
Published: December 2022

ABSTRACT
The World Intellectual Property Organization (WIPO) has enhanced global cooperation in a key area of International Economic Law. In particular, WIPO’s international intellectual property (IP) treaties have done much to bridge the territorial nature of IP with the business needs of innovators and brand owners who operate in an interconnected global economy. They also vividly illustrate the benefits of multilateral cooperation: IP can flow from anywhere to everywhere, thus requiring a truly global approach toward cooperation. Here, we explain some of the practical benefits of WIPO’s Patent Cooperation Treaty, Madrid, and Hague Systems, especially over the last 25 years. Their success has made these systems even more attractive to IP users worldwide and has transformed WIPO’s international filing mechanisms into a truly global endeavor.
Arterial-colonic fistula secondary to colonic stent erosion into the left external iliac artery
Authors: Dillon Jacquelyn , Mills Alexandra N , Pawloski Kate R , Scribetta Nicholas , Greenstein Alexander 
Published: December 2022

Abstract
Self-expandable metal stent (SEMS) are widely utilized as a bridge to surgical intervention and for palliative treatment of malignant bowel obstructions. The risk of complications associated with SEMS is low in well-selected patients. Stent erosion is a rare but serious adverse event that is associated with high morbidity and mortality. Here, we report the case of a 74-year-old patient with a colonic obstruction secondary to a pelvic mass that was treated with SEMS and radiotherapy, who developed a partial thickness stent erosion and recurrent hematochezia 6 years after placement. Endoscopic retrieval was not technically feasible. During attempted surgical resection, massive hemorrhage occurred from a colonic-arterial fistula to the left external iliac artery resulting in death. While SEMS remain an effective, minimally invasive approach for the management of bowel obstructions, prolonged in-situ lifetime may confer an increased risk of serious adverse events including erosion and fistula formation.
Mechanisms of PARP1 inhibitor resistance and their implications for cancer treatment
Authors: Jackson Lindsey M , Moldovan George-Lucian 
Published: December 2022

Abstract
The discovery of synthetic lethality as a result of the combined loss of PARP1 and BRCA has revolutionized the treatment of DNA repair-deficient cancers. With the development of PARP inhibitors, patients displaying germline or somatic mutations in BRCA1 or BRCA2 were presented with a novel therapeutic strategy. However, a large subset of patients do not respond to PARP inhibitors. Furthermore, many of those who do respond eventually acquire resistance. As such, combating de novo and acquired resistance to PARP inhibitors remains an obstacle in achieving durable responses in patients. In this review, we touch on some of the key mechanisms of PARP inhibitor resistance, including restoration of homologous recombination, replication fork stabilization and suppression of single-stranded DNA gap accumulation, as well as address novel approaches for overcoming PARP inhibitor resistance.
Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma
Authors: Carneiro Benedito A , Papadopoulos Kyriakos P , Strickler John H , Lassman Andrew B , Waqar Saiama N , Chae Young Kwang , Patel Jyoti D , Shacham-Shmueli Einat , Kelly Karen , Khasraw Mustafa , Bestvina Christine M , Merrell Ryan , Huang Kevin , Atluri Harisha , Ansell Peter , Li Rachel , Jin Janet , Anderson Mark G , Reilly Edward B , Morrison-Thiele Gladys , Patel Kalpesh , Robinson Randy R , Aristide Martha R Neagu , Gan Hui K 
Published: December 2022

AbstractBackgroundSerclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression.MethodsEligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5–50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma (n = 24); additional assessments included all treated patients.ResultsSixty-two patients (median age: 58 years) were enrolled within the dose-escalation (n = 43) and dose-expansion (n = 19) phases. One dose-limiting toxicity, grade 3 aspartate aminotransferase and alanine aminotransferase elevation, occurred at 20 μg/kg during dose escalation. The Ser-T RP2D regimen of 50 μg/kg × 1 (loading dose) followed by 25 μg/kg Q4W (maintenance dose) was administered during dose expansion. Fatigue (37%) was the only treatment-emergent adverse event (AE) occurring in &gt;25% of patients. Two patients (3%) reported mild treatment-related ocular AEs (eye pruritus). Responses in patients with glioblastoma included 1 partial response (~33 months), 6 stable disease, and 14 progressive disease (not evaluable: n = 3).ConclusionsSer-T monotherapy at doses up to 50 μg/kg initial dose, followed by 25 μg/kg Q4W demonstrated a tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma. The glioblastoma dose-expansion cohort was closed due to a lack of efficacy (NCT03234712).
Predictors of Seeking Care for Influenza-Like Illness in a Novel Digital Study
Authors: Chawla Devika , Benitez Alejandra , Xu Hao , Whitehill Victoria , Tadesse-Bell Sara , Shapiro Allison , Ramirez Ernesto , Scherer Kelly , Foschini Luca , Drawnel Faye , Clinch Barry , Prunotto Marco , Ukachukwu Vincent 
Published: December 2022

Abstract

Background
Previous research has estimated that &gt;50% of individuals experiencing influenza-like illness (ILI) do not seek health care. Understanding factors influencing care-seeking behavior for viral respiratory infections may help inform policies to improve access to care and protect public health. We used person-generated health data (PGHD) to identify factors associated with seeking care for ILI.

Methods
Two observational studies (FluStudy2020, ISP) were conducted during the United States 2019–2020 influenza season. Participants self-reported ILI symptoms using the online Evidation platform. A log-binomial regression model was used to identify factors associated with seeking care.

Results
Of 1667 participants in FluStudy2020 and 47 480 participants in ISP eligible for analysis, 518 (31.1%) and 11 426 (24.1%), respectively, sought health care. Participants were mostly female (92.2% FluStudy2020, 80.6% ISP) and aged 18–49 years (89.6% FluStudy2020, 89.8% ISP). In FluStudy2020, factors associated with seeking care included having health insurance (risk ratio [RR], 2.14; 95% CI, 1.30–3.54), more severe respiratory symptoms (RR, 1.53; 95% CI, 1.37–1.71), and comorbidities (RR, 1.37; 95% CI, 1.20–1.58). In ISP, the strongest predictor of seeking care was high symptom number (RR for 6/7 symptoms, 2.14; 95% CI, 1.93–2.38).

Conclusions
Using PGHD, we confirmed low rates of health care–seeking behavior for ILI and show that having health insurance, comorbidities, and a high symptom burden were associated with seeking health care. Reducing barriers in access to care for viral respiratory infections may lead to better disease management and contribute to protecting public health.
Persistent Symptoms and Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Not Requiring Hospitalization: Results From Testing Denmark, a Danish Cross-sectional Survey
Authors: van Wijhe Maarten , Fogh Kamille , Ethelberg Steen , Karmark Iversen Kasper , Nielsen Henrik , Østergaard Lars , Andersen Berit , Bundgaard Henning , Jørgensen Charlotte S , Scharff Bibi F SS , Ellermann-Eriksen Svend , Johansen Isik S , Fomsgaard Anders , Grove Krause Tyra , Wiese Lothar , Fischer Thea K , Mølbak Kåre , Benfield Thomas , Folke Fredrik , Lippert Freddy , Ostrowski Sisse R , Koch Anders , Erikstrup Christian , Vangsted Anne-Marie , Sørensen Anna Irene Vedel , Ullum Henrik , Skov Robert Leo , Simonsen Lone , Nielsen Susanne Dam 
Published: December 2022

Abstract

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms (“long COVID”). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection.

Methods
In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)–associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score–weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome.

Results
In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2–27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0–7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5–14.6]) and smell (OR, 11.2 [95% CI, 9.1–13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of −2.5 (95% CI, −3.1 to −1.8) and −2.0 (95% CI, −2.7 to −1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID.

Conclusions
Nonhospitalized SARS-CoV-2 PCR–positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.