bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in nerve growth factor in vastus lateralis muscle after the first versus second bout of one‐leg eccentric cycling
Authors: Koeda Tomoko , Mavropalias Georgios , Mizumura Kazue , Katanosaka Kimiaki , Nosaka Kazunori 
Published: September 2023

AbstractDelayed onset muscle soreness (DOMS) develops after performing unaccustomed eccentric exercises. Animal studies have shown that DOMS is mechanical hyperalgesia through nociceptor sensitization induced by nerve growth factor (NGF) and glial cell line‐derived neurotrophic factor (GDNF) upregulated by cyclooxygenase‐2 (COX‐2). However, no previous study has investigated these in relation to DOMS in humans. This study compared the first and second bouts of one‐leg eccentric cycling (ECC) for changes in NGF, GDNF, and COX‐2 mRNA in the vastus lateralis (VL). Seven healthy adults (18–40 years) performed two bouts of ECC (10 sets of 50 contractions) with 80% maximal voluntary concentric peak torque separated by 2 weeks (ECC1, ECC2). Muscle soreness that was assessed by a visual analog scale and maximal voluntary isometric contraction (MVC) torque of the knee extensors were measured before, immediately after (MVC only), 24 and 48 h post‐exercise. Muscle biopsy was taken from the VL before the first bout from nonexercised leg (control) and 24 h after each bout from the exercised leg, and analyzed for NGF, GDNF, and COX‐2 mRNA. Peak DOMS was more than two times greater and MVC torque at 48 h post‐exercise was approximately 20% smaller after ECC1 than ECC2 (p < 0.05), suggesting the repeated bout effect. NGF mRNA level was higher (p < 0.05) post‐ECC1 (0.79 ± 0.68 arbitrary unit) than control (0.06 ± 0.07) and post‐ECC2 (0.08 ± 0.10). GDNF and COX‐2 mRNA did not show significant differences between control, post‐ECC1, and post‐ECC2. These results suggest that an increase in NGF is associated with the development of DOMS in humans.
Gut microbiota and acne: A Mendelian randomization study
Authors: Cao Qiurui , Guo Jinyan , Chang Shuangqing , Huang Zhifang , Luo Qinghua 
Published: September 2023

AbstractBackgroundPrior observational studies have identified a relationship between the composition of gut microbiota and the onset of acne. To ascertain the causal relationship underlying this association, we adopted the Mendelian randomization (MR) method, which offers a powerful approach to causal inference.MethodsSummary statistics on gut microbiota and acne were obtained from the MiBioGen and FinnGen consortium, respectively. The causal relationship was assessed using multiple methods in a two‐sample framework, including MR Egger, weighted median, inverse variance weighted (IVW), and weighted mode. Furthermore, the heterogeneity and horizontal pleiotropy analyses were conducted, along with the leave‐one‐out method.ResultsThe IVW estimation indicated that Allisonella (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.18–1.70, p = 0.0002) and Bacteroides (OR = 2.25, 95% CI = 1.48–3.42, p = 0.0001) have adverse effects on acne. By contrast, Ruminococcus torques group (OR = 0.41, 95% CI = 0.25–0.65, p = 0.0002) showed a beneficial effect on acne. In addition, Candidatus soleaferrea (OR = 0.75, 95% CI = 0.60–0.95, p = 0.0149), Eubacterium coprostanoligenes group (OR = 0.67, 95% CI = 0.47–0.95, p = 0.0230), Fusicatenibacter (OR = 0.71, 95% CI = 0.52–0.97, p = 0.02897), and Lactobacillus (OR = 0.72, 95% CI = 0.58–0.90, p = 0.0046) showed suggestive associations with acne.ConclusionThe present investigation suggests a causal effect of gut microbiota on acne.
An analysis of quality of life and functional outcomes as reported in randomized trials for red cell transfusions
Authors: Pagano Monica B. , Dennis Jane A. , Idemudia Osaumwense M. , Stanworth Simon J. , Carson Jeffrey L. 
Published: September 2023

AbstractBackgroundMeta‐analyses of randomized controlled trials (RCTs) evaluating thresholds for red blood cell (RBC) transfusion typically focus on mortality; however, other outcomes are highly relevant. The aim of this study is to summarize the effects of different transfusion thresholds on the outcomes of quality of life (QoL) and function.Study DesignWe extracted data from RCTs identified in a recently published Cochrane systematic review. Primary analysis was descriptive.ResultsA total of 23 RCTs with 13,743 adult participants were included. Fifteen RCTs included patients in the postoperative period, of which 9 RCTs were conducted in hip (n = 3024) and 6 (n = 8672) in cardiac surgeries; 5 RCTs (n = 489) were in patients with hematological malignancies; 2 in the setting of bleeding (gastrointestinal bleed [n = 936] and postpartum [n = 521]); and one RCT (n = 936) included critically ill patients. QoL and function were reported using a variety of questionnaires and tools. The timing of assessments varied between trials. No clear clinical differences in QoL outcomes were identified in comparisons between restrictive and liberal transfusion thresholds.DiscussionThere is no evidence that a liberal transfusion strategy improves QoL and functional outcomes. However, the substantial limitations of many included studies indicate the need for further well‐designed and adequately powered trials.
Sensitivity of osteosarcoma cell lines to autophagy inhibition as determined by pharmacologic and genetic manipulation
Authors: Gustafson Daniel L. , Viola Lindsey O. , Towers Christina G. , Das Sunetra , Duval Dawn L. , Van Eaton Kristen M. 
Published: September 2023

AbstractPharmacologic inhibition of autophagy can be achieved using lysosomotropic agents such as hydroxychloroquine (HCQ) that interfere with fusion of the autophagosome to the lysosome thus preventing completion of the recycling process. The goal of the present study is to determine the sensitivity of eight canine (cOSA) and four human (hOSA) osteosarcoma tumour cell lines to antiproliferative and cytotoxic effects of lysosomal autophagy inhibitors, and to compare these results to the autophagy‐dependence measured using a CRISPR/Cas9 live‐cell imaging assay in OSA and other tumour cell lines. Antiproliferative and cytotoxic response to HCQ and Lys05 was determined using live cell imaging and YOYO‐1 staining. CRISPR/Cas9 live cell imaging screen was done using species specific guide RNA's and transfection of reagents into cells. Response to autophagy core genes was compared to response to an essential (PCNA) and non‐essential (FOXO3A) gene. cOSA and hOSA cell lines showed similar antiproliferative and cytotoxic responses to HCQ and Lys05 with median lethal dose (Dm) values ranging from 4.6–15.8 μM and 2.1–5.1 μM for measures of anti‐proliferative response, respectively. A relationship was observed between antiproliferative responses to HCQ and Lys05 and VPS34 CRISPR score with Dm values correlating with VPS34 response (r = 0.968 and 0.887) in a species independent manner. The results show that a subset of cOSA and hOSA cell lines are autophagy‐dependent and sensitive to HCQ at pharmacologically‐relevant exposures.
The D129L protein of African swine fever virus interferes with the binding of transcriptional coactivator p300 and IRF3 to prevent beta interferon induction
Authors: Zhang Kehui , Ge Hailiang , Zhou Pingping , Li Lian-Feng , Dai Jingwen , Cao Hongwei , Luo Yuzi , Sun Yuan , Wang Yanjin , Li Jiaqi , Yu Shaoxiong , Li Su , Qiu Hua-Ji 
Published: September 2023

ABSTRACT

African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly lethal swine disease, against which there is no vaccine available except in Vietnam. ASFV has developed multiple strategies to evade the antiviral innate immune responses. Here, we revealed that the D129L protein (pD129L), a nonstructural protein of ASFV, counteracted the type I interferon (IFN) responses and IFN-stimulated genes (ISGs) expression. Furthermore, we demonstrated that knockdown of
D129L
by specific small interfering RNAs enhanced the transcription of IFN-
β
mRNA in the ASFV-infected primary porcine alveolar macrophages (PAMs). Mechanistically, pD129L did not affect the expression of adaptors in the cGAS-STING signaling pathway or the nuclear translocation of IFN regulatory factor 3 (IRF3). Importantly, pD129L specifically bound to the transcriptional coactivators CBP/p300 in the nucleus and inhibited the interaction of IRF3 with CBP/p300, which in turn suppressed the activation of the
IFN-β
promoter to antagonize the IFN-
β
induction. More specifically, the HrcA domain of pD129L and the IRF3-binding domain of p300 were mapped crucial for their interaction. Taken together, our findings demonstrate a novel immunoevasion mechanism evolved by ASFV to escape the host antiviral response, which provides a new target for the development of antiviral strategies.

IMPORTANCE
African swine fever (ASF) is an acute, hemorrhagic, and severe porcine infectious disease caused by African swine fever virus (ASFV). ASF outbreaks severely threaten the global pig industries and result in serious economic losses. No safe and efficacious commercial vaccine is currently available except in Vietnam. To date, large gaps in the knowledge concerning viral biological characteristics and immunoevasion strategies have hindered the ASF vaccine design. In this study, we demonstrate that pD129L negatively regulates the type I interferon (IFN) signaling pathway by interfering with the interaction of the transcriptional coactivator p300 and IRF3, thereby inhibiting the induction of type I IFNs. This study reveals a novel immunoevasion strategy employed by ASFV, shedding new light on the intricate mechanisms for ASFV to evade the host immune responses.
Virome of high-altitude canine digestive tract and genetic characterization of novel viruses potentially threatening human health
Authors: Jiang Xiaojie , Liu Jia , Xi Yuan , Zhang Qing , Wang Yongshun , Zhao Min , Lu Xiang , Wu Haisheng , Shan Tongling , Ni Bin , Zhang Wen , Ma Xiao 
Published: September 2023

ABSTRACT
The majority of currently emerging infectious illnesses are zoonotic infections, which have caused serious public health and economic implications. The development of viral metagenomics has helped us to explore unknown viruses. We collected 1,970 canine feces from Yushu and Guoluo in the plateau region of China for this study to do a metagenomics analysis of the viral community of the canine digestive tract. Our analysis identified 203 novel viruses, classified into 11 known families and 2 unclassified groups. These viruses include the hepatitis E virus, first identified in dogs, and the astrovirus, coronavirus, polyomavirus, and others. The relationship between the newly identified canine viruses and known viruses was investigated through the use of phylogenetic analysis. Furthermore, we demonstrated the cross-species transmission of viruses and predicted new viruses that may cause diseases in both humans and animals, providing technical support for the prevention and control of diseases caused by environmental pollution viruses.

IMPORTANCE
Most emerging infectious diseases are due to zoonotic disease agents. Because of their effects on the security of human or animal life, agriculture production, and food safety, zoonotic illnesses and livestock diseases are of worldwide significance. Because dogs are closely related to humans and domestic animals, they serve as one of the important links in the transmission of zoonotic and livestock diseases. Canines can contaminate the environment in which humans live such as water and soil through secretions, potentially altering the human gut microbiota or causing diseases. Our study enriched the viral community in the digestive tract microbiome of dogs and found types of viruses that threaten human health, providing technical support for the prevention and control of early warning of diseases caused by environmental contaminant viruses.
Gut microbiota of an Amazonian fish in a heterogeneous riverscape: integrating genotype, environment, and parasitic infections
Authors: Leroux Nicolas , Sylvain Francois-Etienne , Holland Aleicia , Luis Val Adalberto , Derome Nicolas 
Published: September 2023

ABSTRACT

A number of key factors can structure the gut microbiota of fish such as environment, diet, health state, and genotype.
Mesonauta festivus
, an Amazonian cichlid, is a relevant model organism to study the relative contribution of these factors on the community structure of fish gut microbiota.
M. festivus
has well-studied genetic populations and thrives in rivers with drastically divergent physicochemical characteristics. Here, we collected 167 fish from 12 study sites and used 16S and 18S rRNA metabarcoding approaches to characterize the gut microbiome structure of
M. festivus
. These data sets were analyzed in light of the host fish genotypes (genotyping-by-sequencing) and an extensive characterization of environmental physico-chemical parameters. We explored the relative contribution of environmental dissimilarity, the presence of parasitic taxa, and phylogenetic relatedness on structuring the gut microbiota. We documented occurrences of
Nyctotherus
sp. infecting a fish and linked its presence to a dysbiosis of the host gut microbiota. Moreover, we detected the presence of helminths which had a minor impact on the gut microbiota of their host. In addition, our results support a higher impact of the phylogenetic relatedness between fish rather than environmental similarity between sites of study on structuring the gut microbiota for this Amazonian cichlid. Our study in a heterogeneous riverscape integrates a wide range of factors known to structure fish gut microbiomes. It significantly improves understanding of the complex relationship between fish, their parasites, their microbiota, and the environment.

IMPORTANCE

The gut microbiota is known to play important roles in its host immunity, metabolism, and comportment. Its taxonomic composition is modulated by a complex interplay of factors that are hard to study simultaneously in natural systems.
Mesonauta festivus
, an Amazonian cichlid, is an interesting model to simultaneously study the influence of multiple variables on the gut microbiota. In this study, we explored the relative contribution of the environmental conditions, the presence of parasitic infections, and the genotype of the host on structuring the gut microbiota of
M. festivus
in Amazonia. Our results highlighted infections by a parasitic ciliate that caused a disruption of the gut microbiota and by parasitic worms that had a low impact on the microbiota. Finally, our results support a higher impact of the genotype than the environment on structuring the microbiota for this fish. These findings significantly improve understanding of the complex relationship among fish, their parasites, their microbiota, and the environment.
Characterization of 29 newly isolated bacteriophages as a potential therapeutic agent against IMP-6-producing
Klebsiella pneumoniae
from clinical specimens
Authors: Kondo Kohei , Nakano Satoshi , Hisatsune Junzo , Sugawara Yo , Kataoka Michiyo , Kayama Shizuo , Sugai Motoyuki , Kawano Mitsuoki 
Published: September 2023

ABSTRACT

Carbapenemase-producing
Enterobacteriaceae
(CPE) are one of the most detrimental species of antibiotic-resistant bacteria globally. Phage therapy has emerged as an effective strategy for the treatment of CPE infections. In western Japan, the rise of
Klebsiella pneumoniae
strains harboring the pKPI-6 plasmid encoding
bla
IMP-6
is of increasing concern. To address this challenge, we isolated 29 phages from Japanese sewage, specifically targeting 31
K
.
pneumoniae
strains and one
Escherichia coli
strain harboring the pKPI-6 plasmid. Electron microscopy analysis revealed that among the 29 isolated phages, 21 (72.4%), 5 (17.2%), and 3 (10.3%) phages belonged to myovirus, siphovirus, and podovirus morphotypes, respectively. Host range analysis showed that 18
Slopekvirus
strains within the isolated phages infected 25–26
K
.
pneumoniae
strains, indicating that most of the isolated phages have a broad host range. Notably,
K. pneumoniae
strain Kp21 was exclusively susceptible to phage øKp_21, whereas Kp22 exhibited susceptibility to over 20 phages. Upon administering a phage cocktail composed of 10 phages, we observed delayed emergence of phage-resistant bacteria in Kp21 but not in Kp22. Intriguingly, phage-resistant Kp21 exhibited heightened sensitivity to other bacteriophages, indicating a “trade-off” for resistance to phage øKp_21. Our proposed phage set has an adequate number of phages to combat the
K. pneumoniae
strain prevalent in Japan, underscoring the potential of a well-designed phage cocktail in mitigating the occurrence of phage-resistant bacteria.

IMPORTANCE

The emergence of
Klebsiella pneumoniae
harboring the
bla
IMP-6
plasmid poses an escalating threat in Japan. In this study, we found 29 newly isolated bacteriophages that infect
K. pneumoniae
strains carrying the pKPI-6 plasmid from clinical settings in western Japan. Our phages exhibited a broad host range. We applied a phage cocktail treatment composed of 10 phages against two host strains, Kp21 and Kp22, which displayed varying phage susceptibility patterns. Although the phage cocktail delayed the emergence of phage-resistant Kp21, it was unable to hinder the emergence of phage-resistant Kp22. Moreover, the phage-resistant Kp21 became sensitive to other phages that were originally non-infective to the wild-type Kp21 strains. Our study highlights the potential of a well-tailored phage cocktail in reducing the occurrence of phage-resistant bacteria.
Chronic wounds in a multiethnic Asian population: a cost of illness study
Authors: Graves Nicholas , Ganesan Ganga , Tan Kelvin Bryan , Goh Orlanda QM , Ho Jackie , Chong Tze Tec , Bishnoi Priya , Carmody David , Yuh Ang Shin , Ng Yi Zhen , Lo Zhiwen , Enming Yong , Abu Bakar Aloweni Fazila , Zifei Wang , Harding Keith 
Published: September 2023

ObjectiveTo estimate the ‘cost of illness’ arising from chronic wounds in Singapore.DesignIncidence-based cost of illness study using evidence from a range of sources.SettingSingapore health services.ParticipantsWe consider 3.49 million Singapore citizens and permanent residents. There are 16 752 new individuals with a chronic wound in 2017, with 598 venous ulcers, 2206 arterial insufficiency ulcers, 6680 diabetic ulcers and 7268 pressure injuries.Primary outcome measures expressed in monetary terms are the value of all hospital bed days lost for the population; monetary value of quality-adjusted life years (QALYs) lost in the population; costs of all outpatient visits; and costs of all poly clinic, use of Community Health Assist Scheme (CHAS) and emergency departments (EDs) visits. Intermediate outcomes that inform the primary outcomes are also estimated.ResultsTotal annual cost of illness was $350 million (range $72–$1779 million). With 168 503 acute bed days taken up annually (range 141 966–196 032) that incurred costs of $139 million (range 117–161 million). Total costs to health services were $184 million (range $120–$1179 million). Total annual costs of lost health outcomes were 2077 QALYs (range −2657 to 29 029) valued at $166 million (range −212 to 2399 million).ConclusionsThe costs of chronic wounds are large to Singapore. Costs can be reduced by making positive investments for comprehensive wound prevention and treatment programmes.
Prevalence and phenotypic trajectories of hypoxaemia among hospitalised adults in Kenya: a single-centre, prospective cohort study
Authors: Navuluri Neelima , Lagat David K , Birgen Elcy , Kitur Sylvia , Kussin Peter S , Murdoch David M , Thielman Nathan M , Parish Alice , Green Cynthia L , MacIntyre Neil , Egger Joseph R , Wools-Kaloustian Kara , Que Loretta G 
Published: September 2023

ObjectiveGlobal medical oxygen security is limited by knowledge gaps in hypoxaemia burden and oxygen access in low-income and middle-income countries. We examined the prevalence and phenotypic trajectories of hypoxaemia among hospitalised adults in Kenya, with a focus on chronic hypoxaemia.DesignSingle-centre, prospective cohort study.SettingNational tertiary referral hospital in Eldoret, Kenya between September 2019 and April 2022.ParticipantsAdults (age ≥18 years) admitted to general medicine wards.Primary and secondary outcome measuresOur primary outcome was proportion of patients who were hypoxaemic (oxygen saturation, SpO2 ≤88%) on admission. Secondary outcomes were proportion of patients with hypoxaemia on admission who had hypoxaemia resolution, hospital discharge, transfer, or death among those with unresolved hypoxaemia or chronic hypoxaemia. Patients remaining hypoxaemic for ≤3 days after admission were enrolled into an additional cohort to determine chronic hypoxaemia. Chronic hypoxaemia was defined as an SpO2 ≤ 88% at either 1-month post-discharge follow-up or, for patients who died prior to follow-up, a documented SpO2 ≤88% during a previous hospital discharge or outpatient visit within the last 6 months.ResultsWe screened 4104 patients (48.5% female, mean age 49.4±19.4 years), of whom 23.8% were hypoxaemic on admission. Hypoxaemic patients were significantly older and more predominantly female than normoxaemic patients. Among those hypoxaemic on admission, 33.9% had resolution of their hypoxaemia as inpatients, 55.6% had unresolved hypoxaemia (31.0% died before hospital discharge, 13.3% were alive on discharge and 11.4% were transferred) and 10.4% were lost to follow-up. The prevalence of chronic hypoxaemia was 2.1% in the total screened population, representing 8.8% of patients who were hypoxaemic on admission. Chronic hypoxaemia was determined at 1-month post-discharge among 59/86 patients and based on prior documentation among 27/86 patients.ConclusionHypoxaemia is highly prevalent among adults admitted to a general medicine ward at a national referral hospital in Kenya. Nearly 1 in 11 patients who are hypoxaemic on admission are chronically hypoxaemic.