bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiating necrotizing soft tissue infections from cellulitis by soft tissue infectious fluid analysis: a pilot study
Authors: Wu Kai-Hsiang , Wu Po-Han , Chang Chih-Yao , Kuo Yen-Ting , Hsiao Kuang-Yu , Hsiao Cheng-Ting , Hung Shang-Kai , Chang Chia-Peng 
Published: January 2022

Abstract
Background
We conducted this study to evaluate the characteristics of the infectious fluid in soft tissue infection and investigate the utility of the biochemical tests and Gram stain smear of the infectious fluid in distinguishing necrotizing soft tissue infection (NSTI) from cellulitis.

Methods
This retrospective cohort study was conducted in a tertiary care hospital in Taiwan. From April 2019 to October 2020, patients who were clinically suspected of NSTI with infectious fluid accumulation along the deep fascia and received successful ultrasound-guided aspiration were enrolled. Based on the final discharge diagnosis, the patients were divided into NSTI group, which was supported by the surgical pathology report, or cellulitis group. The t test method and Fisher’s exact test were used to compare the difference between two groups. The receiver–operator characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the discriminating ability.

Results
Total twenty-five patients were enrolled, with 13 patients in NSTI group and 12 patients in cellulitis group. The statistical analysis showed lactate in fluid (AUC = 0.937) and LDH in fluid (AUC = 0.929) had outstanding discrimination. The optimal cut-off value of fluid in lactate was 69.6 mg/dL with corresponding sensitivity of 100% and specificity of 76.9%. The optimal cut-off value of fluid in LDH was 566 U/L with corresponding sensitivity of 83.3% and a specificity of 92.3%. In addition, albumin in fluid (AUC = 0.821), TP in fluid (AUC = 0.878) and pH in fluid (AUC = 0.858) also had excellent diagnostic accuracy for NSTI. The Gram stain smear revealed 50% bacteria present in NSTI group and all the following infectious fluid culture showed bacteria growth.

Conclusions
The analysis of infectious fluid along the deep fascia might provide high diagnostic accuracy to differentiate NSTI from cellulitis.
Permanent His-bundle pacing in the right atrium in a patient with a Mobitz II atrioventricular block: a case presentation
Authors: Zhang Zai-Qiang , Ding Jia-Wang 
Published: January 2022

Abstract
Background
This case report presents a patient diagnosed with sick sinus syndrome who was successfully treated with permanent His-bundle pacing (PHBP).

Case presentation
A 36-year-old man was transferred to our hospital due to recurrent syncope. He was diagnosed with sick sinus syndrome based on the 24-h Holter and a history of syncope. He was admitted to hospital and successfully treated with PHBP. The postoperative examination showed that the pacing rhythm, pacemaker pacing and perception function were normal. He was discharged without any complications after a successful pacemaker implantation.

Conclusions
We described a case in which PHBP may become an optimal approach to the management of patients with sick sinus syndrome. Right ventricular pacing has been attempted with inconsistent efficacy outcomes. HBP provides a promising alternative pacing option that might provide symptom resolution to patients with sick sinus syndrome.
Thoracoscopic infrared ablation to create a box lesion as a treatment for atrial fibrillation
Authors: Kubota Hiroshi , Ohtsuka Toshiya , Ninomiya Mikio , Nonaka Takahiro , Hisagi Motoyuki , Endo Hidehito , Minegishi Sachito , Tsuchiya Hiroshi , Inaba Yusuke 
Published: January 2022

Abstract
Background
Creating a box lesion in the posterior wall of the left atrium from the epicardial side of the beating heart remains a challenge. Although a transmural lesion can be created by applying radiofrequency (RF) energy at clampable sites, it is still difficult to create a transmural lesion at unclampable sites because the inner blood flow in the unclampable free wall weakens the thermal effect on the outside. Our aim was to apply the newly developed infrared coagulator to create linear transmural lesions on the beating heart thoracoscopically to treat atrial fibrillation (AF).

Case presentation
A 71-year-old male was referred to our hospital with a diagnosis of hypertrophic cardiomyopathy and permanent atrial fibrillation. The patient was first diagnosed with atrial fibrillation 20 years before. Direct current cardioversion had been performed every few years a total of four times, but sinus rhythm restoration had always been temporary. On February 27, 2020, thoracoscopic PV isolation together with infrared roof- and bottom-line ablation to create a box lesion and left atrial appendage amputation (LAAA) were performed. The coagulator could be applied to clinical thoracoscopic surgery to successfully create a box lesion without any complication. The patient restored a regular sinus rhythm, it has been maintained for eleven months, and there have been no adverse events.

Conclusions
The infrared coagulator might have enough potential to create transmural lesions on the beating heart in thoracoscopic AF surgery.
The PID Life Index: an interactive tool to measure the status of the PID healthcare environment in any given country
Authors: Solís Leire , Nordin Julia , Prevot Johan , Mahlaoui Nizar , Sánchez-Ramón Silvia , Ali Adli , Cassignol Elodie , Seymour John W. , Pergent Martine 
Published: January 2022

Abstract
Background
The “Primary Immunodeficiencies (PIDs) principles of care” were published in 2014 as the gold standard for care of patients with PIDs, setting a common goal for stakeholders to ensure that patients with PID have access to appropriate care and good quality of life. Since then, IPOPI (the International Patient Organisation for Primary Immunodeficiencies), has been working with national PID patient organisations as well as collaborating with scientific and medical institutions and experts to bring these principles closer to the day-to-day life of individuals with PIDs.

Method
The six PID Principles of Care were revised to consider advances in the field, as well as political developments that had occurred after their initial publication in 2014. Based on this revision the list was updated, and a new principle was added. The six established principles were: diagnosis, treatment, universal health coverage, specialised centres, national patient organisations and registries. Each principle was structured and measured through a series of criteria, and was given the same weight, as they have been considered to all be equally important. Specific weights were attributed to the criteria depending on their relevance and importance to quantify the principle. The index was translated into a survey for data collection: initially involving data from selected countries for a pilot, followed by integration of data from IPOPI’s national member organisations and key countries.

Results
The PID Life Index was developed in 2020 to assess the status of the PID environment and the implementation of the 6 principles worldwide. The Index allows for benchmarking countries either according to a set of principles and criteria or based on the user’s preferences. This can be displayed in an interactive map or through a data visualisation system.

Conclusion
The PID Life Index has been developed successfully and has potential to become an important source of information for PID stakeholders, to increase awareness and information as well as support advocacy initiatives on PIDs nationally, regionally or globally.
ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer
Authors: Dong Shuohui , Liang Shuo , Cheng Zhiqiang , Zhang Xiang , Luo Li , Li Linchuan , Zhang Wenjie , Li Songhan , Xu Qian , Zhong Mingwei , Zhu Jiankang , Zhang Guangyong , Hu Sanyuan 
Published: January 2022

Abstract
Background
Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined.

Methods
Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro.

Results
The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU.

Conclusions
HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.
Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy
Authors: Saliakoura Maria , Sebastiano Matteo Rossi , Nikdima Ioanna , Pozzato Chiara , Konstantinidou Georgia 
Published: January 2022

Abstract
Background
KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer.

Methods
To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the KrasG12D/+;p53flox/flox;Pdx1-CreERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice.

Results
Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment.

Conclusions
Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells.
Sugar-sweetened beverage consumption and breast composition in a longitudinal study of Chilean girls
Authors: Yoon Lara , Corvalán Camila , Pereira Ana , Shepherd John , Michels Karin B. 
Published: January 2022

Abstract
Background
Frequent sugar-sweetened beverage (SSB) intake has been associated with indirect markers of breast cancer risk, such as weight gain in adolescents and early menarche. How SSB intake relates to breast composition in adolescent girls has not been explored.

Methods
We evaluated the association between prospective intake of SSB and breast density in a cohort of 374 adolescent girls participating in the Growth and Obesity Cohort Study in Santiago, Chile. Multivariable linear regression models were used to analyze the association between average daily SSB intake quartiles and breast composition (absolute fibroglandular volume [aFGV], percent fibroglandular volume [%FGV], total breast volume [tBV]). Models were adjusted for potential confounding by BMI Z-score, age, daily energy intake (g/day), maternal education, hours of daily television watching after school, dairy intake (g/day), meat intake (g/day), waist circumference, and menarche. To examine the sensitivity of the association to the number of dietary recalls for each girl, analyses were further stratified by girls with one dietary recall and girls with > one dietary recall.

Results
A total of 881 dietary recalls were available for 374 girls prior to the breast density assessment. More than 60% of the cohort had > one dietary recall available. In multivariable analyses, we found no association between SSB intake quartile and aFGV (Q2 vs Q1 β: − 5.4, 95% CI − 15.1, 4.4; Q3 vs Q1 β: 1.3, 95% CI − 8.6, 11.3; Q4 vs Q1 β: 3.0, 95% CI − 7.1, 13). No associations were noted for %FGV and tBV. Among girls with at least one dietary recall, we found no significant associations between SSB intake quartiles and %FGV, aFGV, or tBV.

Conclusion
Overall, we observed no evidence that SSB intake was associated with breast density in adolescent Chilean girls.
Genicular artery embolization as a novel treatment for mild to moderate knee osteoarthritis: protocol design of a randomized sham-controlled clinical trial
Authors: van Zadelhoff T. A. , Moelker A. , Bierma-Zeinstra S. M. A. , Bos P. K. , Krestin G. P. , Oei E. H. G. 
Published: January 2022

Abstract
Introduction
Knee osteoarthritis is a common disease with pain as the most prevalent symptom. Previous cohort studies have shown genicular artery embolization to reduce pain symptoms in patients with mild to moderate knee osteoarthritis. Patients resistant to conservative therapy but not eligible yet for surgical treatment due to young age or comorbidities may profit from an effective and sustained pain reduction treatment. This study is a randomized sham-controlled trial to evaluate the efficacy of genicular artery embolization in patients with knee osteoarthritis.

Methods and analysis
Fifty-eight patients with mild-to-moderate knee osteoarthritis will be recruited and randomly allocated to the treatment or control group in a 1:1 ratio. Participants in the treatment group will undergo genicular artery embolization. Patients in the control group will undergo sham treatment. Outcome measurements will be assessed at baseline and after 1, 4, 8, and 12 months with questionnaires, pressure pain threshold testing, and MR imaging. The MR imaging protocol is designed to (semi)quantitatively assess osteoarthritis in the knee joint. The primary outcome is the change from baseline of the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale after 4 months. Secondary outcomes include change in osteoarthritis-related questionnaires, pressure pain threshold, and OA-related MRI features, particularly synovitis and bone marrow lesions.

Ethics and dissemination
This trial will determine the efficacy of genicular artery embolization compared to a sham treatment. This is of importance to assess before proceeding to larger-scale efficiency studies and, ultimately, implementing this treatment into day to day clinical practice.

Trial registration
ClinicalTrials.gov NCT03884049. Registered on 21 March 2019
Cytauxzoon europaeus infections in domestic cats in Switzerland and in European wildcats in France: a tale that started more than two decades ago
Authors: Willi Barbara , Meli Marina L. , Cafarelli Chiara , Gilli Urs O. , Kipar Anja , Hubbuch Alina , Riond Barbara , Howard Judith , Schaarschmidt Daniel , Regli Walter , Hofmann-Lehmann Regina 
Published: January 2022

Abstract
Background
Cytauxzoon spp. infection is believed to be a newly emerging tick-borne disease in felids in Europe, with three species of the haemoparasite having recently been differentiated in wild felids. In Switzerland, rare infections have been documented in domestic cats in the west and northwest of the country, the first of which was in 2014. The aims of the present study were: (i) to characterize a Cytauxzoon spp. hotspot in domestic cats in central Switzerland; (ii) to elucidate the geographic distribution of Cytauxzoon spp. in domestic cats in Switzerland; (iii) to assess suspected high-risk populations, such as stray and anaemic cats; and (iv) to investigate the newly emerging nature of the infection. Cytauxzoon spp. were further differentiated using mitochondrial gene sequencing.

Methods
The overall study included samples from 13 cats from two households in central Switzerland (study A), 881 cats from all regions of Switzerland (study B), 91 stray cats from a hotspot region in the northwest of Switzerland and 501 anaemic cats from across Switzerland (study C), and 65 Swiss domestic cats sampled in 2003 and 34 European wildcats from eastern France sampled in the period 1995–1996 (study D). The samples were analysed for Cytauxzoon spp. using real-time TaqMan quantitative PCR, and positive samples were subjected to 18S rRNA, cytochrome b (CytB) and cytochrome c oxidase subunit I (COI) gene sequencing.

Results
In study A, six of 13 cats from two neighbouring households in central Switzerland tested postive for Cytauxzoon spp.; two of the six infected cats died from bacterial infections. In studies B and C, only one of the 881 cats (0.1%; 95% confidence interval [CI]: 0–0.3%) in the countrywide survey and one of the 501 anaemic cats (0.2%; 95% CI: 0–0.6%) tested postive for Cytauxzoon spp. while eight of the 91 stray cats in the northwest of Switzerland tested positive (8.8%; 95% CI: 3.0–14.6%). In study D, Cytauxzoon spp. was detected in one of the 65 domestic cat samples from 2003 (1.5%; 95% CI: 0–4.5%) and in ten of the 34 European wildcat samples from 1995 to 1996 (29%; 95% CI: 14.2–44.7%). The isolates showed ≥ 98.6% sequence identities among the 18S rRNA, CytB and COI genes, respectively, and fell in the subclade Cytauxzoon europaeus based on CytB and COI gene phylogenetic analyses.

Conclusions
The study challenges the newly emerging nature of Cytauxzoon spp. in central Europe and confirms that isolates from domestic cats in Switzerland and European wild felids belong to the same species.

Graphical Abstract
Insecticidal efficacy against Phlebotomus perniciosus in dogs treated orally with fluralaner in two different parallel-group, negative-control, random and masked trials
Authors: Bongiorno Gioia , Meyer Leon , Evans Alec , Lekouch Nouha , Doherty Padraig , Chiummo Rafael , Gradoni Luigi 
Published: January 2022

Abstract
Background
Dogs are the reservoir host of Leishmania infantum, the agent of zoonotic visceral leishmaniasis (VL), which is transmitted by the bite of phlebotomine sand flies. The sand fly Phlebotomus perniciosus is the main vector of zoonotic VL in the western Mediterranean region. Fluralaner has been shown to effectively kill this vector. The aim of this study was to evaluate the insecticidal efficacy of oral fluralaner in dogs bitten by P. perniciosus.

Methods
Two parallel-group, negative-controlled, randomized, masked laboratory trials with equivalent designs were performed in two different locations using two different pathogen-free laboratory-bred P. perniciosus strains for the challenge. In each trial, 12 purpose-bred beagles, initially ranked on natural attractiveness to sand flies, were randomly allocated to two groups (6 animals/group). Dogs in one group received fluralaner orally at the approved dose on day 0, and dogs in the control group were not treated. Each dog was subsequently exposed to an average of 70 unfed live sand fly females on days 1, 28, 56 and 84. Viability of blood-fed females was then evaluated for up to 96 h after exposure, and insecticidal efficacy was measured as the survival rate of flies fed on the fluralaner-treated dogs versus that of dogs in the control group. Significance was calculated for the proportion of live fed sand fly counts from treated versus control group dogs.

Results
Comparison of the survival proportions between treated and control groups showed that fluralaner insecticidal efficacy was highly significant in both trials (P < 0.001 or P < 0.01 in different assessments) through to day 56. In the first trial, efficacy reached 100% on days 1 and 28, and 99.1% on day 56; in the second trial, the insecticidal efficacy was 98.5, 100 and 85.9%, respectively on the same days. On day 84, efficacy was in the range of 53–57% (P < 0.05) in the first trial and 0% in the second trial.

Conclusion
A single oral fluralaner administration to dogs under laboratory conditions results in strong and reproducible insecticidal efficacy against P. perniciosus for at least 8 weeks.

Graphical Abstract
Characterization of Anopheles gambiae D7 salivary proteins as markers of human–mosquito bite contact
Authors: Oseno Brenda , Marura Faith , Ogwang Rodney , Muturi Martha , Njunge James , Nkumama Irene , Mwakesi Robert , Mwai Kennedy , Rono Martin K. , Mwakubambanya Ramadhan , Osier Faith , Tuju James 
Published: January 2022

AbstractBackgroundMalaria is transmitted when infectedAnophelesmosquitoes take a blood meal. During this process, the mosquitoes inject a cocktail of bioactive proteins that elicit antibody responses in humans and could be used as biomarkers of exposure to mosquito bites. This study evaluated the utility of IgG responses to members of theAnopheles gambiaeD7 protein family as serological markers of human–vector contact.MethodsThe D7L2, D7r1, D7r2, D7r3, D7r4 and SG6 salivary proteins fromAn. gambiaewere expressed as recombinant antigens inEscherichia coli. Antibody responses to the salivary proteins were compared in Europeans with no prior exposure to malaria and lifelong residents of Junju in Kenya and Kitgum in Uganda where the intensity of malaria transmission is moderate and high, respectively. In addition, to evaluate the feasibility of using anti-D7 IgG responses as a tool to evaluate the impact of vector control interventions, we compared responses between individuals using insecticide-treated bednets to those who did not in Junju, Kenya where bednet data were available.ResultsWe show that both the long and short forms of the D7 salivary gland antigens elicit a strong antibody response in humans. IgG responses against the D7 antigens reflected the transmission intensities of the three study areas, with the highest to lowest responses observed in Kitgum (northern Uganda), Junju (Kenya) and malaria-naïve Europeans, respectively. Specifically, the long form D7L2 induced an IgG antibody response that increased with age and that was lower in individuals who slept under a bednet, indicating its potential as a serological tool for estimating human–vector contact and monitoring the effectiveness of vector control interventions.ConclusionsThis study reveals that D7L2 salivary antigen has great potential as a biomarker of exposure to mosquito bites and as a tool for assessing the efficacy of vector control strategies such as bednet use.Graphical abstract