bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment strategies to reduce cardiovascular risk in persons with chronic kidney disease and Type 2 diabetes
Authors: Zannad Faiez , McGuire Darren K. , Ortiz Alberto
Published: December 2024

Chronic kidney disease (CKD) is a prevalent and progressive condition associated with significant mortality and morbidity. Diabetes is a common cause of CKD, and both diabetes and CKD increase the risk of cardiovascular disease (CVD), the leading cause of death in individuals with CKD. This review will discuss the importance of early detection of CKD and prompt pharmacological intervention to slow CKD progression and delay the development of CVD for improving outcomes.

Early CKD is often asymptomatic, and diagnosis usually requires laboratory testing. The combination of estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio (UACR) measurements is used to diagnose and determine CKD severity. Guidelines recommend at least annual screening for CKD in at‐risk individuals. While eGFR testing rates are consistently high, rates of UACR testing remain low. This results in underdiagnosis and undertreatment of CKD, leaving many individuals at risk of CKD progression and CVD. UACR testing is an actionable component of the CKD definition.

A four‐pillar treatment approach for slowing the progression of diabetic kidney disease is suggested, comprising a renin–angiotensin–system (RAS) inhibitor, a sodium–glucose cotransporter 2 inhibitor, a glucagon‐like peptide 1 receptor agonist, and the nonsteroidal mineralocorticoid receptor antagonist finerenone. The combination of these agents provides a greater cardiorenal risk reduction compared with RAS inhibitors alone.

Early detection of CKD and prompt intervention with guideline‐directed medical therapy are crucial for reducing CVD risk in individuals with CKD and diabetes. Evidence from ongoing studies will advance our understanding of optimal therapy in this population.
Protective Effects of Spondias mombin L. Juice Alone or in Combination With Lactobacillus acidophilus in 5‐Fluorouracil‐Induced Experimental Intestinal Mucositis
Authors: Barbosa Stphannie Jamyla de Araújo , Oliveira Maisie Mitchele Barbosa , Ribeiro Susana Barbosa , Silva Rafaela Alcindo , de Medeiros Caroline Addison Carvalho Xavier , Guerra Gerlane Coelho Bernardo , Júnior Raimundo Fernandes de Araújo , de Sousa Junior Francisco Canindé , Martins Agnes Andrade , Ferreira Leandro De Santis , Pinheiro Francisco Ayrton Senna Domingos , Rebouças Conceição S. Martins , de Castro Brito Gerly Anne , Leitao Renata Ferreira Carvalho , Andrade Raphael Victor Silva , de Araujo Valkleidson Santos , de Araújo Aurigena Antunes
Published: December 2024

Background

Evaluate the impact of Spondias mombin L. juice (SM), alone and in combination with Lactobacillus acidophilus, in an experimental model of intestinal mucositis.

Methods

Swiss mice were orally administered with saline, SM, or SM combined with L. acidophilus NRRL B‐4495 at 1 × 109 colony‐forming unit (CFU/mL) for 15 days before the induction of intestinal mucositis by a single intraperitoneal injection of 5‐fluorouracil (5‐FU) at 450 mg/kg. On the 18th day, following euthanasia, tissue samples were collected for histopathological examination. Jejunum tissues were analyzed for MUC‐2 immunoexpression, concentrations of interleukin‐1‐beta (IL‐1β), interleukin 6 (IL‐6) and tumor necrosis factor (TNF)‐α, and invertase activity.

Key Results

5‐FU induced intestinal damage in all intestinal segments, and this damage involved villus blunting, flattened and vacuolated cells, crypt necrosis, inflammatory cell infiltration, and mucosa and submucosal edema compared to the control group. In contrast, SM or SM with L. acidophilus prevented these morphological alterations in all intestinal segments (p < 0.05). Both treatments reduced the intestinal concentration of IL‐1 beta (p < 0.05), IL‐6 (p < 0.05), and TNF‐alpha (p < 0.05). Notably, the combination of SM and L. acidophilus, but not SM alone, prevented the 5‐FU‐induced decrease in invertase activity and mucin expression (p < 0.05). Furthermore, SM combined with L. acidophilus resulted in an increased population of lactic acid bacteria in feces on the 7th and 18th days. Combining SM with L. acidophilus also decreased fecal excretion of γ‐Ergostenol and γ‐sitosterol.

Conclusions and Inferences

SM, alone and combined with Lactobacillus acidophilus demonstrated significant protective effects against 5‐FU‐induced intestinal mucositis, reducing inflammatory markers.
Symptom Patterns in Adults With Cyclic Vomiting Syndrome: A 6‐Month Prospective Observational Study
Authors: Chen Yaozhu J. , Rodriguez Danielle , Richmond Camilla A. , Hasler William L. , Levinthal David J. , Li B. U. K. , Petrakis Ioannis , Coyne Karin S. , Wu Melody , Tack Jan , Venkatesan Thangam
Published: December 2024

Background

Data are limited on the natural history and symptom patterns of cyclic vomiting syndrome (CVS), a disorder of gut–brain interaction characterized by recurrent stereotypical vomiting, retching, and nausea episodes.

Methods

A 6‐month, observational, remote study prospectively assessed symptom patterns in adults with CVS using an electronic daily diary. Patients recorded their disease experience, including CVS symptoms and associated severity, in the daily diary. The study defined a CVS episode start as the first day of 5 or more vomiting and/or retching (V + R) events. Episode end was defined as the first day of ≥ 7 (prespecified main analysis) or ≥ 4 (sensitivity analysis) days without any diary V + R events.

Key Results

Eighty‐eight of 93 (94.6%) enrolled patients (62 female; mean age, 37.7 years) had daily diary data recorded during the study; 61 (69.3%) patients had at least one episode. In the prespecified main analysis, 191 episodes (median, 0.6 per 30 diary days) were reported (median duration, 3.0 days); 17.8% of the episodes lasted > 10 days. In the sensitivity analysis, 248 episodes (median, 0.7 per 30 diary days) were reported (median duration, 2.0 days). Thirteen of 88 (14.8%) patients with diary data had interepisodic V + R (reported V + R events without meeting the threshold for study‐defined episode). Other CVS‐related (non‐V + R) symptoms (most frequently nausea, abdominal pain, and sweating) were reported more frequently during the episode versus the interepisodic period.

Conclusions and Inferences

This prospective longitudinal study shows marked heterogeneity of CVS episodes and highlights the need to better define and characterize episodes in these patients.
Future Applications of Central Neuromodulation and Neurophysiological Testing in Cyclic Vomiting Syndrome
Authors: Levinthal David J. , Kuo Braden
Published: December 2024

Background

Cyclic vomiting syndrome (CVS) is defined by its episodic patterning. Furthermore, CVS is associated with other episodic disorders such as migraine and epilepsy. Indeed, many of the medications that are known to be useful for prophylaxis and abortive therapy in CVS are also effective in preventing and aborting migraines and seizures. These observations strongly suggest that CVS has a neural basis, but the precise pathophysiological mechanisms that operate in CVS remain unclear.

Purpose

This brief review describes recent neurophysiological insights and opportunities to further advance the understanding of pathophysiological neural mechanisms that are present in patients with CVS. These insights are poised to translate into the next generation of neurotherapeutic strategies for CVS using central neuromodulation. Additionally, the development of neurophysiological tests of neural excitability could be positioned to shape management decisions in future CVS care.
The Impact of COVID‐19 on Oil and Natural Gas Production
Authors: Ben Salah Sarra , Moussaoui Hana
Published: December 2024

The COVID‐19 pandemic has significantly impacted global economies, disrupting various sectors, including energy production. This study examines the effects of COVID‐19 on oil and natural gas production in 14 producer countries between January 2020 and December 2021. Using the generalised method of moments (GMM) and panel data analysis, we explore the relationship between pandemic‐related disruptions, energy prices and trade openness on the production of non‐renewable energy sources. Results indicate that COVID‐19 negatively influenced both oil and gas production, with a stronger impact observed on oil. While trade openness positively contributed to energy production, rising energy prices exacerbated the decline in output. The findings underscore the importance of resilience strategies, including robust energy policies and adaptive measures, to mitigate the effects of future global crises. This research contributes to the literature by providing comprehensive insights into the production challenges and opportunities within the energy sector during a pandemic.
Childhood and Adolescent Overweight/Obesity Prevalence Trends in Jiangsu, China, 2017–2021: An Age‐Period‐Cohort Analysis
Authors: Yu Jinxia , Chen Sunan , Yang Jie , Zhang Xiyan , Xue Hui , Ni Xiaoyan , Du Wei , Fan Lijun , Zhang Fengyun , Wang Yan
Published: December 2024

Objectives

To investigate temporal trends in childhood and adolescent overweight/obesity in Jiangsu Province, China, evaluating the effects of age, period, and birth cohort.

Design

Cross‐sectional study.

Sample

Participants were 210,168 students aged 6–17 years from the five waves of the consecutive cross‐sectional Jiangsu provincial surveillance project in 2017–2021.

Measurements

Overweight/obesity was assessed according to the sex‐ and age‐specific body mass index. We used age‐period‐cohort (APC) analysis to explore the temporal trends of overweight/obesity and to estimate the effects of age, period, and birth cohort on the prevalence.

Results

The overall prevalence of overweight/obesity has increased from 32.08% to 38.60% between 2017 and 2021. The 6–9‐year‐old group and the 10–13‐year‐old group were significantly associated with a higher risk of overweight/obesity, in contrast to 14–17‐year‐olds. The pandemic was also significantly associated with a much higher risk. The cohort 2000–2003 was associated with higher risk, and such association continued until the cohort 2012–2015, denoting a significantly lower risk.

Conclusions

Despite an increasing trend in the prevalence of overweight/obesity, especially during the COVID‐19 pandemic, the latest cohort effect was significantly associated with a lower risk. We recommend continuous efforts on preventive interventions and more research about prevalence trends.
High levels of REV7 expression are associated with poor prognosis and chemoresistance in gastric adenocarcinoma
Authors: Kesen Yurika , Ichinoe Masaaki , Hayashi Shoko , Umezawa Atsuko , Numata Yoshiko , Kogami Taro , Matsushita Masahiro , Sanoyama Itaru , Hoshino Akiyoshi , Sakurai Yasutaka , Kato Takuya , Murakumo Yoshiki
Published: December 2024

REV7 is a multifunctional protein essential for promoting cellular tolerance to DNA damage. REV7 expression is associated with disease progression and prognosis in several human malignant tumors. This study aimed to evaluate the clinical and biological significance of REV7 in gastric adenocarcinoma (GAD). REV7 expression in 167 resected GADs was immunohistochemically assessed and examined the association with clinicopathological features. Positive expression of REV7 was significantly associated with tumor undifferentiation (p < 0.001), lymphatic invasion (p = 0.035), recurrence (p = 0.042), and mortality (p = 0.031). The Kaplan‐Meier curves with log‐rank tests revealed significantly poorer progression‐free survival (p = 0.049), overall survival (p = 0.037), and post‐progression survival (p = 0.038) in the REV7‐positive group. Multivariate analysis using the Cox proportional hazard model identified REV7 as an independent prognostic factor for overall survival (p = 0.028). REV7‐depleted GAD cell lines demonstrated enhanced sensitivity to cisplatin compared with control cells. Additionally, the expression levels of REV7 in residual tumors from surgical specimens of patients who received preoperative chemotherapy were higher than those in samples without chemotherapy (p = 0.029), suggesting that REV7‐positive tumors are chemoresistant. These results indicate that REV7 is a predictive biomarker for the prognosis and chemosensitivity of GAD.
Phylogenomic insights into the relationship and the evolutionary history of planthoppers (Insecta: Hemiptera: Fulgoromorpha)
Authors: Deng Junchen , Stroiński Adam , Szwedo Jacek , Ghanavi Hamid Reza , Yapar Etka , Franco Diego Castillo , Prus‐Frankowska Monika , Michalik Anna , Wahlberg Niklas , Łukasik Piotr
Published: December 2024

Planthoppers (Hemiptera: Fulgoromorpha) are a species‐rich and globally distributed insect clade with high economic, ecological and evolutionary importance. However, the relationships among planthopper lineages and families remain unclear. Previous efforts based on inconsistent morphological traits, a few genes or limited sampling often resulted in conflicting tree topologies. Here, we used genome‐level data to assemble 1164 nuclear single‐copy genes and 13 mitochondrial protein‐coding genes for 149 planthopper species representing 19 out of 21 extant families. Additional markers were added from published mitogenomes, expanding our sampling to 285 species. These markers were used for maximum likelihood–based tree inference and dating analyses. The newly inferred phylogenies validated well‐accepted relationships and recovered novel placements for several taxa, including the family Achilixiidae and species from the tribe Lyncidini and genus Madagascaritia in Dictyopharidae and Fulgoridae. Based on molecular and morphological evidence, we proposed taxonomic changes including the establishment of a new family Borysthenidae stat. rev. within Delphacoidea and a new superfamily Meenoploidea superfam. nov. with redefined Kinnaridae stat. rev. and Meenoplidae stat. rev. The time analyses based on 57 nuclear markers and 30 fossils dated the origin of extant Fulgoromorpha back to Guadalupian, Permian (~263 Ma), close to the maximum constraint at 267.3 Ma, while applying an older root constraint resulted in an origin in Mississippian, Carboniferous (~332 Ma). While future sampling of unstudied fauna in unexplored regions or habitats may change the topology, the current phylogenomic analysis will serve as a solid foundation for research into planthopper ecology, evolution and significance.
TaqMan Array Card real‐time polymerase chain reaction panel to detect pathogens in whole blood of febrile inpatients in northern Tanzania, 2016–2019
Authors: Ngocho James S. , Liu Jie , Kalengo Nathaniel H. , Kipengele Asia H. , Maro Athanasia , Mujage Buliga , Senyael Ndealilia , Gratz Jean , Kilonzo Kajiru G. , Kinabo Grace , Lwezaula Bingileki F. , Lyamuya Furaha , Marandu Annette , Mbwasi Ronald , Mmbaga Blandina T. , Mosha Calvin , Carugati Manuela , Madut Deng B. , Bonnewell John P. , Maze Michael J. , Maro Venance P. , Crump John A. , Houpt Eric R. , Rubach Matthew P.
Published: December 2024

Background

Acute febrile illness is a common reason for seeking healthcare in low‐ and middle‐income countries. We describe the diagnostic utility of a TaqMan Array Card (TAC) real‐time polymerase chain reaction (PCR) panel for pathogen detection in paediatric and adult inpatients admitted with febrile illness.

Methods

In this prospective cohort study, we screened medical admissions for a tympanic temperature ≥38.0°C or reported fever within 72 h and used a PCR panel to detect pathogens, including bacteria, viruses, fungi and protozoa, in 697 participants. We compared PCR results to conventional diagnostic methods and considered PCR detections as the cause of fever, except for Plasmodium spp. and Schistosoma spp. Participants for PCR testing was consecutively selected from the end of enrolment.

Results

Of 1132 participants enrolled in the cohort, 697 (61.6%) were tested by PCR. Median (IQR) age was 29.6 (4.6–46.4) years. Three hundred seventy‐eight (54.2%) were male. The PCR method improved illness identification, increasing diagnostic yield from 73 (10.5%) by conventional methods to 124 (17.8%) of 697 participants. PCR detections included four viral pathogens: dengue (n = 1), enterovirus (n = 7), measles (n = 1) and Rift Valley Fever Virus (RVFV) (n = 3). Forty‐six bacterial pathogens were detected in 44 (6.3%) participants, including fastidious bacteria such as Bartonella spp. (n = 2), Brucella spp. (n = 3), Coxiella burnetii (n = 2), Leptospira spp. (n = 1), M. tuberculosis (n = 7) and Rickettsia spp. (n = 9).

Conclusion

The PCR panel improved pathogen detection in febrile inpatients, providing clinically actionable results for fastidious bacteria and epidemiologically relevant findings like RVFV detections, when combined with conventional methods.
Alterations in the autonomic and haemodynamic response to prolonged high‐intensity endurance exercise in individuals with coronary artery calcification
Authors: Svane Jakob , Wiktorski Tomasz , Eftestøl Trygve , Ørn Stein
Published: December 2024

Endurance exercise is associated with increased life duration and improved life quality. Paradoxically, high exercise intensity is also associated with increased coronary artery calcification (CAC) and a small but significant increased risk of adverse cardiac events during exercise. The mechanisms underlying the development of CAC during prolonged high‐intensity endurance exercise are unknown. This study aims to determine if there are differences in cardiovascular haemodynamic measures and heart rate variability (HRV) in individuals with (CAC+) and without CAC (CAC−). Hemodynamic measures from 56 healthy, middle‐aged (median [interquartile range] 51 [43–58] years) individuals (41 men/15 women) participating in a 91 km [251.2 [217.2‐271.6] min] leisure sport mountain bike race were included in this study. Twenty‐five participants (20 men/5 women) were classified as CAC+ based on coronary computed tomographic assessment. Haemodynamic measures and HRV were quantified at the top of the hardest hill (THH) during the last quarter of the race. At the top of THH, CAC+ individuals had significantly higher systolic blood pressure (SBP) (235 [225–245] mmHg vs. 220 [193–238] mmHg, P = 0.008), higher diastolic blood pressure (DBP) (105 [95–110] mmHg vs. 95 [85–110] mmHg, P = 0.006), higher pulse pressure (130 [125–140] mmHg vs. 123 [110–130] mmHg, P = 0.039), higher mean rate pressure product (33,882 [30,872–35,053] bpm × mmHg vs. 31,028 [27,392–33,047] bpm × mmHg, P = 0.028), and larger increase in DBP from baseline (20 [20–30] mmHg vs. 10 [0–20] mmHg, P = 0.001), compared with CAC− individuals. Further, CAC+ participants showed a significant reduction in the low‐frequency component of HRV (HRVLF) (6.3 [2.4–11.5] ms2 vs. 12.4 [6.8–20.2] ms2, P = 0.044). In multivariable analysis, HRVLF was an independent predictor of the presence of CAC even after adjusting for established risk factors of atherosclerosis: age, sex, body mass index, maximum heart rate, , smoking, resting SBP and resting DBP. CAC+ individuals had significant alterations in haemodynamic measures and HRVLF following prolonged high‐intensity endurance exercise compared with individuals without CAC. HRVLF was an independent predictor of CAC, suggesting an adverse autonomic response to high‐intensity endurance exercise in individuals with CAC.
The relationship between channel interaction, electrode placement, and speech perception in adult cochlear implant users
Authors: Berg Katelyn , Goldsworthy Ray , Noble Jack , Dawant Benoit , Gifford René
Published: December 2024

This study (1) characterized the effects of channel interaction using spectral blurring, (2) evaluated an image-guided electrode selection (IGES) method aiming to reduce channel interaction, and (3) investigated the impact of electrode placement factors on the change in performance by condition. Twelve adult MED-EL (Innsbruck, Austria) cochlear implant recipients participated. Performance was compared across six conditions: baseline (no blurring), all blurred, apical blurred, middle blurred, basal blurred, and IGES. Electrode placement information was calculated from post-insertion computerized tomography (CT) imaging. Each condition tested measures of speech recognition and subjective ratings. Results showed poorer performance when spectral blurring was applied to all channels compared to baseline, suggesting an increase in channel interaction was achieved. Vowel recognition was more sensitive to apical and middle blurring while consonant recognition was more sensitive to basal blurring, indicating that phoneme identification may be useful for assessing channel interaction clinically. IGES did not significantly improve group performance, and electrode placement factors did not impact results. However, participants who were more affected by spectral blurring tended to benefit more from IGES. These findings indicate that spectral blurring can help identify areas most affected by channel interaction to help optimize electrode selection.
Comparative Effects of the Free Weights and Smith Machine Squat and Bench Press: The Important Role of Specificity for Strength Adaptations
Authors: Marcos-Frutos Daniel , Miras-Moreno Sergio , Márquez Gonzalo , García-Ramos Amador
Published: December 2024

Purpose: Although previous studies have compared strength-training adaptations between free weights (FW) and machine-guided exercises, those studies did not use a Smith machine (SM), which most closely replicates the exercises performed with FW. Thus, the aim of the present study was to investigate the chronic effects of strength-focused, velocity-based training regimens using FW versus SM. Methods: Thirty-seven sport-science students (14 female) were assigned, balanced by sex and relative strength, to either an FW or SM training group. The training program lasted 8 weeks (2 sessions/wk), and participants performed 4 sets per exercise (back squat and bench press) at 70% of their 1-repetition maximum with moderate effort levels (20%–25% velocity loss). Load–velocity profile parameters (load-axis intercept, velocity-axis intercept, and area under the load–velocity relationship line), cross-sectional areas of the vastus lateralis and pectoralis major muscles, and the number of repetitions to failure in the bench-press exercise were assessed before and after the training program. Mechanical variables were assessed using both FW and SM. Results: All variables, with the exception of back-squat velocity-axis intercept (P = .124), improved in both training groups. The changes in load-axis intercept and area under the load–velocity relationship line were more pronounced when the training and testing conditions matched. Failure in the bench-press exercise and cross-sectional areas of the vastus lateralis and pectoralis major showed comparable improvements for both training groups, while velocity-axis intercept tended to improve more in the SM group. Conclusions: The general population, unconcerned with the specificity of strength adaptations, can choose a training modality (FW or SM) based on personal preferences.
Leveraging Resources Through Interdisciplinary Partnerships
Authors: Brusseau Timothy A. , Perrin David H.
Published: December 2024

In 2014, the College of Health at the University of Utah hired a new dean, who was charged with increasing research productivity (e.g., extramural funding). This paper highlights several ways that the Department of Health and Kinesiology (more broadly the College of Health) leveraged resources through interdisciplinary partnerships to meet this challenge. More specifically, the paper highlights efforts to develop new research space, explore partnerships with other units and initiatives on campus to recruit and retain faculty, and use existing programming on campus to strengthen the research infrastructure. It also illustrates changes in policies that enabled this research expansion.
Morphogenetic penicillin-binding proteins control virulence-associated type III secretion systems in
Salmonella
Authors: Castanheira Sónia , Torronteras Sara , Cestero Juan J. , García-del Portillo Francisco
Published: December 2024

Type III protein secretion systems (T3SSs) function as multiprotein devices that span the envelope of Gram-negative bacteria using the peptidoglycan (PG) layer as scaffold. This spatial arrangement explains why modifications in PG structure can alter T3SS activity. In
Salmonella,
incorporation of non-canonical D-amino acids in the PG was shown to decrease the activity of the T3SS encoded by the pathogenicity island-1 (SPI-1) without affecting other T3SS, like the flagellum apparatus. Enigmatically, following invasion of host cell
Salmonella enterica
serovar Typhimurium modifies PG synthesis by upregulating two pathogen-specific enzymes, the penicillin-binding proteins PBP2
SAL
and PBP3
SAL
, with roles in cell elongation and division, respectively. In the mouse typhoid model, the amount of PBP2
SAL
and PBP3
SAL
produced by the pathogen exceeds by large those of the canonical enzymes PBP2 and PBP3. This change responds to acidity and high osmolarity, the same cues that intra-phagosomal
S
. Typhimurium perceives to switch the SPI-1 T3SS by that encoded in SPI-2. Using isogenic mutants lacking each of the four morphogenetic PBPs, we tested whether their activities and those of the T3SS encoded by SPI-1 and SPI-2, are interconnected. Our data show that PBP2 is required for proper function of SPI-1 T3SS but dispensable for motility, whereas the lack of any of the morphogenetic PBPs increases SPI-2 T3SS activity. The positive control exerted by PBP2 on SPI-1 takes place via the SPI-1-specific regulators HilA and InvF. To our knowledge, these findings provide the first evidence linking morphogenetic enzymes that synthesize PG with T3SS associated to virulence.
Prediction of antimicrobial susceptibility of pneumococci based on whole-genome sequencing data: a direct comparison of two genomic tools to conventional antimicrobial susceptibility testing
Authors: Sanchez Gerardo J. , Cuypers Lize , Laenen Lies , Májek Peter , Lagrou Katrien , Desmet Stefanie
Published: December 2024

Determination of antimicrobial resistance (AMR) in pneumococcal isolates is important for surveillance purposes and in a clinical context. Antimicrobial susceptibility testing (AST) of pneumococci is complicated by the need for exact minimal inhibitory concentrations (MICs) of beta-lactam antibiotics. Two next-generation sequencing (NGS) analysis tools have implemented the prediction of AMR in their analysis workflow, including the prediction of MICs: Pathogenwatch (
https://pathogen.watch/
) and AREScloud (OpGen). The performance of these tools in comparison to phenotypic AST following EUCAST guidelines is unknown. A total of 538
Streptococcus pneumoniae
isolates were used to compare both tools with phenotypic AST for penicillin, amoxicillin, cefotaxime/ceftriaxone, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline. Disk diffusion was performed for all isolates, and broth microdilution was performed for isolates with reduced beta-lactam susceptibility. Demultiplexed FASTQ files from Illumina sequencing, covering the whole genome of pneumococci, were used as input for the NGS tools. Categorical agreement (CA), major error (ME), and very major error (VME) rates were calculated. For beta-lactam antibiotics, CA was high (>94%) associated with none or only one ME and VME (<1%). For erythromycin and tetracycline, CA was >93% for predictions by AREScloud, while for Pathogenwatch, this ranged around 88%. For trimethoprim-sulfamethoxazole, CA was for both tools <86%. High VME rates were observed for erythromycin and tetracycline, higher for Pathogenwatch (53.6% and 47.0%, respectively) compared to AREScloud (14.3% and 19.1%, respectively). Both tools performed excellently despite the complexity of predicting beta-lactam resistance in pneumococci. Further optimization and validation are needed for non-beta-lactams since high (very) major error rates were observed.
Characteristics of viral ovarian tumor domain protease from two emerging orthonairoviruses and identification of Yezo virus human infections in northeastern China as early as 2012
Authors: Chen Zi-Yun , Zhang Jie , He Pei-Jun , Xiong Tao , Zhu Dai-Yun , Zhu Wen-Jie , Ni Xue-Bing , Du Li-Feng , Wang Qian , Zhang Ya-Wei , Xia Luo-Yuan , Chen Dong-Sheng , Li Liang-Jing , Zhang Ming-Zhu , Cui Xiao Ming , Wang Tian-Hong , Wang Juan , Wang Zhenfei , An Tian-Feng , Cao Wu-Chun , Liu Xiao-Hua , Huang En-Jiong , Jia Na
Published: December 2024

Emerging tick-borne orthonairovirus infections pose a growing global concern, with limited understanding of the viral ovarian tumor-like cysteine proteases (vOTUs) encoded by novel orthonairoviruses. These vOTUs, a group of deubiquinylases (DUBs), disrupt the innate immune response. Yezo virus (YEZV), a recently discovered pathogenic orthonairovirus, was first reported in Japan in 2021. In this study, we successfully isolated and identified YEZV and a new orthonairovirus, Jiànchuān tick virus (JCTV), from
Ixodes persulcatus
and
Haemaphysalis montgomeryi
ticks, respectively, in China. We found that the vOTU domains encoded by YEZV and JCTV exhibited both DUB and deISGylase activities, though with potentially less broad deISGylation compared to that of Crimean-Congo hemorrhagic fever virus (CCHFV) during natural infection. Phylogenetic analysis of global vOTUs, including 83 new sequences, revealed a high diversity of this domain. Interestingly, retrospective screening of tick-bite patients from 2012 to 2016 in northeastern China traced YEZV infections as far back as 2012, identifying four cases. Additionally, YEZV primarily infected
I. persulcatus
(31.4%) and
Dermacentor nuttalli
(10.5%) in northern China, while JCTV exhibited high infection rates in
H. montgomeryi
(81.3%) in southern China. In summary, our work emphasizes the active surveillance of orthonairovirus infections and the imperative need for the development of vOTU domain-targeted anti-virals, offering potential therapeutic solutions for a broad spectrum of orthonairoviruses.

IMPORTANCE

The vOTUs, a group of DUBs, mimic the functions of host DUBs to enhance viral infectivity and may serve as potential drug targets. vOTUs from different orthonairoviruses exhibit distinct preferences toward ubiquitin (Ub) and ubiquitin-like protein interferon stimulated gene 15 (ISG15). In this study, we investigated the deubiquitinase and deISGylase functions of various orthonairoviral vOTUs using both an overexpression system and natural viral infections
in vitro
. Our findings illustrate that the vOTUs from YEZV and JCTV can cleave both Ub and ISG15 in an overexpression system, but these viruses exhibit potentially narrower deISGylation capacity than CCHFV during natural infection. This suggests that the diversity of vOTUs may have a potential relationship with the pathogenesis.
Induction of innate immunity and plant growth promotion in tomato unveils the antiviral nature of bacterial endophytes against groundnut bud necrosis virus
Authors: Sharanya R. , Gayathri M. , Renukadevi P. , Saranya N. , Suganthy M. , Varanavasiappan S. , Ghosh Amalendu , Nakkeeran S.
Published: December 2024

Tomato is an important crop worldwide, but groundnut bud necrosis virus (GBNV) often hampers its growth. This study investigates the antiviral potential of bacterial endophytes, including
Brucella melitensis
CNEB54,
Bacillus licheniformis
CNEB4,
Bacillus velezensis
CNEB26, and
Bacillus vallismortis
BAVE5 against GBNV, as well as their ability to enhance immunity and growth in tomato. All four bacterial isolates demonstrated a significant delay in GBNV symptom development 10 days post-inoculation, with disease incidence ranging from 18% to 36% compared to 84% in control. DAC-ELISA results indicated a noteworthy reduction in virus titer (0.32–0.96 OD) in treated tomato plants versus the control (3.26 OD). In addition, qPCR analysis revealed decreased viral copy numbers in plants treated with bacterial endophytes (1.3–3.1 × 10
5
) as against in untreated inoculated control (2.4 × 10
6
). Furthermore, these endophytes upregulated the expression of defense-associated genes, such as
MAPKK1
,
PAL
,
PPO
,
LOX1
,
JAR1
, and
PDF 1.2
. Field experiments with the application of
B. melitensis and B. velezensis
exhibited improved growth, with an average plant height of 123.70 cm, 14.87 flowers per plant, and a fruit weight of 549.3 g per plant, with a disease incidence of 18.1%. In comparison, the untreated control plants only reached a height of 104.73 cm, produced 11.17 flowers per plant, and yielded 267 g of fruit per plant, with a disease incidence of 30.1%. These findings strongly support the use of bacterial endophytes to reduce disease incidence and severity, enhance plant immunity and promote plant growth, resulting in overall crop productivity in sustainable agriculture.

IMPORTANCE

The infection of GBNV in crops such as tomatoes, peanuts, and pulses leads to significant yield loss. Applying insecticides to control vector populations, can limit the spread of viruses carried by these vectors. The present study envisages a novel strategy to combat GBNV, with the help of bacterial endophytes. These bacterial endophytes have tremendously reduced the symptom expression of GBNV, induced the expression of defense genes during the tri-trophic interaction and promoted plant growth in tomatoes under field conditions. Hence, these bacteria are identified to be involved in immunity boosting, viral suppression and growth promotion.
Quorum sensing inhibits phage infection by regulating biofilm formation of
P. aeruginosa
PAO1
Authors: Cao Lei , Mi Jinhui , He Yile , Xuan Guanhua , Wang Jingxue , Li Mengzhe , Tong Yigang
Published: December 2024

Quorum sensing (QS) can regulate diverse critical phenotypic responses in
Pseudomonas. aeruginosa
(
P. aeruginosa
), enabling bacterial adaptation to external environmental fluctuations and optimizing population advantages. While there is emerging evidence of QS’s involvement in influencing phage infections, our current understanding remains limited, necessitating further investigation. In this study, we isolated and characterized a novel phage designated as BUCT640 that infected
P. aeruginosa
PAO1. This phage belonged to class
Caudoviricetes
, genus
Bruynoghevirus
, with a podovirus morphology, and its adsorption was dependent on Psl polysaccharides, a repeating pentamer used to support biofilm structure. Leveraging phage BUCT640 as a model, we analyzed the role of both
rhl
QS and
las
QS in bacteria–phage interactions. Based on its distinctive plaque formation performances on different QS-related mutants, we investigated the variations of phage sensitivity to these strains and ultimately elucidated the mechanism underlying how QS inhibited phage infection to PAO1. Specifically, we unveiled that the
las
QS could inhibit phage adsorption, which is related to the thickness change caused by biofilm differentiation. Our findings suggest that the inhibition of QS may enhance phage infectivity, potentially facilitating advanced phage therapy combined with QS interference.

IMPORTANCE

Phage therapy is a powerful solution to combat drug-resistant pathogenic bacterial infections and has earned remarkable success in clinical treatment. However, recent insights underscore the potential impact of bacterial QS on phage infection dynamics. Here, we reported a unique phenomenon wherein QS, particularly in the
las
QS pathway, showed distinctive plaque formation behaviors by enlarging halos around plaques in mutant strains. In addition to this, we first elucidated the correlation between biofilm formation and phage infection. Notably, the
las
QS could inhibit phage adsorption, an effect closely related to biofilm thickness. Such research could be the evidence to steer bacterial QS toward favorable therapeutical outcomes. Therefore, our work can extend the comprehension of the interactions between bacteria and phages influenced by QS, thereby providing new perspectives on leveraging QS interference to enhance the efficacy of phage therapy for clinical applications.
Complete genome sequence of
Pseudoxanthomonas koreensis
strain TDY-1, an odor-reducing bacterium isolated from livestock wastewater
Authors: Han Kook-Il , Nam Young Ho , Kim Eui-Jin
Published: December 2024

We report the complete genome sequence of
Pseudoxanthomonas koreensis
TDY-1
,
an odor-reducing strain isolated from livestock wastewater on a pig farm. Its genome consists of a 2.97-Mb chromosome.
Identification and characterization of
Faecalibacterium
prophages rich in diversity-generating retroelements
Authors: Gulyaeva Anastasia , Liu Lei , Garmaeva Sanzhima , Kruk Marloes , Weersma Rinse K. , Harmsen Hermie J. M. , Zhernakova Alexandra
Published: December 2024

Metagenomics has revealed the incredible diversity of phages within the human gut. However, very few of these phages have been subjected to in-depth experimental characterization. One promising method of obtaining novel phages for experimental characterization is through induction of the prophages integrated into the genomes of cultured gut bacteria. Here, we developed a bioinformatic approach to prophage identification that builds on prophage genomic properties, existing prophage-detecting software, and publicly available virome sequencing data. We applied our approach to 22 strains of bacteria belonging to the genus
Faecalibacterium
, resulting in identification of 15 candidate prophages, and validated the approach by demonstrating the activity of five prophages from four of the strains. The genomes of three active phages were identical or similar to those of known phages, while the other two active phages were not represented in the Viral RefSeq database. Four of the active phages possessed a diversity-generating retroelement (DGR), and one retroelement had two variable regions. DGRs of two phages were active at the time of the induction experiments, as evidenced by nucleotide variation in sequencing reads. We also predicted that the host range of two active phages may include multiple bacterial species. Finally, we noted that four phages were less prevalent in the metagenomes of inflammatory bowel disease patients compared to a general population cohort, a difference mainly explained by differences in the abundance of the host bacteria. Our study highlights the utility of prophage identification and induction for unraveling phage molecular mechanisms and ecological interactions.

IMPORTANCE

While hundreds of thousands of phage genomes have been discovered in metagenomics studies, only a few of these phages have been characterized experimentally. Here, we explore phage characterization through bioinformatic identification of prophages in genomes of cultured bacteria, followed by prophage induction. Using this approach, we detect the activity of five prophages in four strains of commensal gut bacteria
Faecalibacterium
. We further note that four of the prophages possess diversity-generating retroelements implicated in rapid mutation of phage genome loci associated with phage–host and phage–environment interactions and analyze the intricate patterns of retroelement activity. Our study highlights the potential of prophage characterization for elucidating complex molecular mechanisms employed by the phages.
Knowledge, attitudes and practices among patients with impacted wisdom teeth towards teeth extraction in Jinan, Shandong Province, China: a cross-sectional study
Authors: Sun Jing , Meng Junru , Wang Xin , Wang Bing , Luan Xiao , Li Shu , Tong Dongdong
Published: December 2024

Objectives

This study aimed to assess the knowledge, attitudes and practices (KAP) of patients with impacted wisdom teeth towards tooth extraction, with the intention of identifying both gaps and opportunities for improved dental health education and practices.

Design

A cross-sectional study using a web-based questionnaire.

Setting

The study was conducted at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, and Jinan Stomatological Hospital.

Participants

This study included responses from 3467 individuals presenting with impacted wisdom teeth at the study settings between March and May 2023.

Primary and secondary outcome measures

The primary outcomes measured were the levels of KAP towards wisdom teeth extraction among participants. Knowledge was assessed on a scale of 0–11, attitudes on a scale of 10–50 and practices on a scale of 11–55. Secondary outcomes included the exploration of associations between knowledge, attitudes and practices using structural equation modelling.

Results

Participants demonstrated a mean knowledge score of 9.1±1.4, mean attitude score of 38.0±2.7 and mean practice score of 41.7±8.2. The analysis using a structural equation model revealed a direct effect of knowledge on attitudes (path coefficient=2.042, p<0.001) and a direct effect of attitudes on practices (path coefficient=1.460, p<0.001).

Conclusions

The findings suggest that patients with impacted wisdom teeth possess adequate knowledge and favourable attitudes towards teeth extraction, which positively influences their practices. However, tailored interventions are still needed to further enhance KAP regarding this procedure in this population.
Clinical predictors of 3-month isoniazid rifapentine (3HP)-related adverse drug reactions (ADR) during tuberculosis preventive therapy (PAnDoRA-3HP study): an observational study protocol
Authors: Sekaggya-Wiltshire Christine , Mbabazi Irene , Nabisere Ruth Mirembe , Alinaitwe Lucy , Otaalo Brian , Aber Florence , Nampala Juliet , Owori Rogers , Bayigga Josephine , Mayito Jonathan , Banturaki Grace , Laker Eva Agnes Odongpiny , Castelnuovo Barbara , Sekadde Moorine Penninah , Pasipanodya Jotam , Dooley Kelly E , Stavia Turyahabwe , Zawedde‐Muyanja Stella
Published: December 2024

Introduction

Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings.

Methods

This is an observational cohort study with a nested case–control study. We enrolled consecutive patients who had been initiated on TPT using the 3HP regimen. These are followed up biweekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2, AADAC and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes.

Analysis

The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. χ2tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modelling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.

Ethics and dissemination

Ethical approval of this study inclusive of all the appropriate documents was obtained from the Infectious Diseases Institute Research and Ethics Committee and the Uganda National Council of Science and Technology. The study adheres to legal, ethical and Good Clinical Practice (GCP) guidelines. Deidentified genotype data from 300 patients will be shared after publication. The protocol and phenotype data will be publicly accessible. Abstracts will be submitted to conferences, and a manuscript will be published poststudy.
Comparison of neurological outcomes between out-of-hospital cardiac arrest due to anaphylaxis and cardiac causes: a nationwide population-based observational study
Authors: Hirata Kaiho , Chiba Takuyo , Hosono Kazuki , Tsuji Haruka , Ikeda Shunya , Shiga Takashi
Published: December 2024

Objective

To compare the neurological outcomes of out-of-hospital cardiac arrest due to anaphylaxis (OHCA-A) and cardiac causes (OHCA-C).

Design

Retrospective observational study.

Setting

Japanese nationwide dataset from 2012 to 2021.

Participants

In total, 153 890 patients were included in this study, of which 331 had OHCA-A and 153 559 had OHCA-C.

Outcome measures

The primary outcome was a favourable neurological outcome 1 month after cardiac arrest. The secondary outcome was survival at 1 month.

Results

Patients with OHCA-A had a significantly higher favourable neurological outcome rate (24.2% vs 11.7%, p<0.001) and higher survival rate at 1 month (33.2% vs 16.1%, p<0.001) than patients with OHCA-C. Multivariable logistic regression analysis revealed that OHCA-A was associated with higher odds of favourable neurological outcomes (adjusted OR (adj OR): 1.86; 95% CI 1.34 to 2.59) and survival at 1 month (adj OR: 2.43; 95% CI 1.78 to 3.31). Similarly, the propensity score-matched cohort showed favourable neurological outcomes in patients with OHCA-A (OR: 2.91; 95% CI 1.83 to 4.65).

Conclusion

Compared with OHCA-C, OHCA-A is associated with favourable neurological outcomes and warrants more aggressive resuscitation efforts.
Tuberculosis screening among cough suppressant buyers in pharmacies and drug outlets in Guinea: a cross-sectional study
Authors: Magassouba Aboubacar Sidiki , Toure Almamy Amara , Diallo Boubacar Djelo , Camara Gnoume , Dahourou Desire Lucien , Nabe Aly Badara , Camara Souleymane , Bangoura Adama Marie , Traore Hugues Asken , Campbell Jonathon R , Veronese Vanessa , Merle Corinne Simone Collette
Published: December 2024

Background

Tuberculosis (TB) poses a significant public health challenge in Guinea, with an estimated 22 000 TB cases in 2020; an estimated 6125 (28%) cases went undetected. We evaluated an intensified TB case finding strategy in Guinea which targeted customers who bought cough suppressants from pharmacies or drug outlets.

Methods

We involved 25 pharmacies and 25 drug outlets in Matoto, Conakry, Guinea. Pharmacists or outlet owners identified and referred all customers with TB symptoms who were purchasing cough suppressants to healthcare workers for sputum collection either at the pharmacy or drug outlet or at a nearby TB diagnosis and treatment centre (CDT); sputum was subjected to bacteriological testing with acid fast bacilli smear or Xpert MTB/RIF. We assessed factors associated with eventual TB diagnosis using logistic regression and time to TB diagnosis using cox regression and used microcosting to estimate the cost of the intervention in 2020 US$.

Results

From November 2019 to June 2020, we screened 916 people referred from pharmacies or drug outlets with TB symptoms, with median age of 31 years (54% male). Overall, 126 (14%) had bacteriologically confirmed TB. Odds of TB diagnosis were significantly lower with increasing age (adjusted OR (aOR) per additional year=0.98; 95% CI 0.97 to 0.99) and higher among males (aOR=1.57; 95% CI 1.04 to 2.39) and those with symptoms. Those identified at drug outlets had significantly faster time to presentation from symptom onset than pharmacies (adjusted HR=1.73; 95% CI 1.50 to 1.99). The total cost of the intervention per person referred was US$32.66 and per person diagnosed and treated for TB disease of US$237.45.

Conclusion

Intensified TB case finding through pharmacies and drug outlets is a feasible and effective way to increase TB detection in settings where self-medicating is common, and TB is under-detected.