bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification analysis of the 4-Coumarate: CoA ligase (4CL) gene family expression profiles in Juglans regia and its wild relatives J. Mandshurica resistance and salt stress
Authors: Ma Jiayu , Zuo Dongjun , Zhang Xuedong , Li Haochen , Ye Hang , Zhang Nijing , Li Mengdi , Dang Meng , Geng Fangdong , Zhou Huijuan , Zhao Peng
Published: March 2024

Persian walnut (Juglans regia) and Manchurian walnut (Juglans mandshurica) belong to Juglandaceae, which are vulnerable, temperate deciduous perennial trees with high economical, ecological, and industrial values. 4-Coumarate: CoA ligase (4CL) plays an essential function in plant development, growth, and stress. Walnut production is challenged by diverse stresses, such as salinity, drought, and diseases. However, the characteristics and expression levels of 4CL gene family in Juglans species resistance and under salt stress are unknown. Here, we identified 36 Jr4CL genes and 31 Jm4CL genes, respectively. Based on phylogenetic relationship analysis, all 4CL genes were divided into three branches. WGD was the major duplication mode for 4CLs in two Juglans species. The phylogenic and collinearity analyses showed that the 4CLs were relatively conserved during evolution, but the gene structures varied widely. 4CLs promoter region contained multiply cis-acting elements related to phytohormones and stress responses. We found that Jr4CLs may be participated in the regulation of resistance to anthracnose. The expression level and some physiological of 4CLs were changed significantly after salt treatment. According to qRT-PCR results, positive regulation was found to be the main mode of regulation of 4CL genes after salt stress. Overall, J. mandshurica outperformed J. regia. Therefore, J. mandshurica can be used as a walnut rootstock to improve salt tolerance. Our results provide new understanding the potential functions of 4CL genes in stress tolerance, offer the theoretical genetic basis of walnut varieties adapted to salt stress, and provide an important reference for breeding cultivated walnuts for stress tolerance.
Preoperative routine measurement of NT-proBNP predicts postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk: an observational study
Authors: Schmidt Götz , Frieling Nora , Schneck Emmanuel , Habicher Marit , Koch Christian , Rubarth Kerstin , Balzer Felix , Aßmus Birgit , Sander Michael
Published: March 2024

Background

Chronic heart failure (HF) is a common clinical condition associated with adverse outcomes in elderly patients undergoing non-cardiac surgery. This study aimed to estimate a clinically applicable NT-proBNP cut-off that predicts postoperative 30-day morbidity in a non-cardiac surgical cohort.

Methods

One hundred ninety-nine consecutive patients older than 65 years undergoing elective non-cardiac surgery with intermediate or high surgical risk were analysed. Preoperative NT-proBNP was measured, and clinical events were assessed up to postoperative day 30. The primary endpoint was the composite morbidity endpoint (CME) consisting of rehospitalisation, acute decompensated heart failure (ADHF), acute kidney injury (AKI), and infection at postoperative day 30. Secondary endpoints included perioperative fluid balance and incidence, duration, and severity of perioperative hypotension.

Results

NT-proBNP of 443 pg/ml had the highest accuracy in predicting the composite endpoint; a clinical cut-off of 450 pg/ml was implemented to compare clinical endpoints. Although 35.2% of patients had NT-proBNP above the threshold, only 10.6% had a known history of HF. The primary endpoint was the composite morbidity endpoint (CME) consisting of rehospitalisation, acute decompensated heart failure (ADHF), acute kidney injury (AKI), and infection. Event rates were significantly increased in patients with NT-proBNP > 450 pg/ml (70.7% vs. 32.4%, p < 0.001), which was due to the incidence of cardiac rehospitalisation (4.4% vs. 0%, p = 0.018), ADHF (20.1% vs. 4.0%, p < 0.001), AKI (39.8% vs. 8.3%, p < 0.001), and infection (46.3% vs. 24.4%, p < 0.01). Perioperative fluid balance and perioperative hypotension were comparable between groups. Preoperative NT-proBNP > 450 pg/ml was an independent predictor of the CME in a multivariable Cox regression model (hazard ratio 2.92 [1.72–4.94]).

Conclusions

Patients with NT-proBNP > 450 pg/ml exhibited profoundly increased postoperative morbidity. Further studies should focus on interdisciplinary approaches to improve outcomes through integrated interventions in the perioperative period.

Trial registration

German Clinical Trials Register: DRKS00027871, 17/01/2022
Time to death and its predictors among adult patients on mechanical ventilation admitted to intensive care units in West Amhara comprehensive specialized hospitals, Ethiopia: a retrospective follow-up study
Authors: Demem Kenubish , Tesfahun Esubalew , Nigussie Fetene , Shibabaw Aster Tadesse , Ayenew Temesgen , Messelu Mengistu Abebe
Published: March 2024

Introduction

Mechanical ventilation is the most common intervention for patients with respiratory failure in the intensive care unit. There is limited data from African countries, including Ethiopia on time to death and its predictors among patients on mechanical ventilators. Therefore, this study aimed to assess time to death and its predictors among adult patients on mechanical ventilation admitted in comprehensive specialized hospitals in West Amhara, Ethiopia.

Methods

An institutional-based retrospective follow-up study was conducted from January 1, 2020, to December 31, 2022. A simple random sampling was used to select a total of 391 patients’ charts. Data were collected using data the extraction tool, entered into Epi-data version 4.6.0, and exported to STATA version 14 for analysis. Kaplan–Meier failure curve and the log-rank test were fitted to explore the survival difference among groups. The Cox regression model was fitted, and variables with a p-value < 0.25 in the bivariable Cox regression were candidates for the multivariable analysis. In the multivariable Cox proportional hazard regression, an adjusted hazard ratio with 95% confidence intervals were reported to declare the strength of association between mortality and predictors when a p value is < 0.05.

Results

A total of 391 mechanically ventilated patients were followed for 4098 days at risk. The overall mortality of patients on mechanical ventilation admitted to the intensive care units was 62.2%, with a median time to death of 16 days (95% CI: 11, 22). Those patients who underwent tracheostomy procedure (AHR = 0.40, 95% CI: 0.20, 0.80), received cardio-pulmonary resuscitation (AHR = 8.78, 95% CI: 5.38, 14.35), being hypotensive (AHR = 2.96, 95% CI: 1.11, 7.87), and had a respiratory rate less than 12 (AHR = 2.74, 95% CI: 1.48, 5.07) were statistically significant predictors of time to death among mechanically ventilated patients.

Conclusion

The mortality rate of patients on mechanical ventilation was found to be high and the time to death was short. Being cardiopulmonary resuscitated, hypotensive, and had lower respiratory rate were significant predictors of time to death, whereas patients who underwent tracheostomy was negatively associated with time to death. Tracheostomy is needed for patients who received longer mechanical ventilation, and healthcare providers should give a special attention for patients who are cardiopulmonary resuscitated, hypotensive, and have lower respiratory rate.
A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM]
Authors: Gibson David , Vo Anh Huan , Lambing Hannah , Bhattacharya Prithanjan , Tahir Peggy , Chehab Farid F. , Butowski Nicholas
Published: March 2024

Background

MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.

Methods

To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.

Results

We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG’s 70–90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG’s 73–89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG’s 8, 19, 22, 25, 27, 32,38, and CpG sites 21–37, as well as low methylation level of the enhancer regions.

Conclusion

The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Clinical application of middle descending colon-double lumen ostomy with distal stoma narrowing in the treatment of anorectal malformation
Authors: Huang Guoxian , Li Wenni , Ma Lili , Lei Xin , Lin Xiangde , Chen Yuandong , Xu Bo
Published: March 2024

Background

Anorectal malformations (ARMs) are the most common congenital anomaly of the digestive tract. And colostomy should be performed as the first-stage procedure in neonates diagnosed with intermediate- or high-type ARMs. However, the most classic Pe˜na’s colostomy still has some disadvantages such as complicated operation procedure, susceptibility to infection, a greater possibility of postoperative incision dehiscence, difficulty of nursing and large surgical trauma and incision scarring when closing the stoma. We aimed to explore the effectiveness of middle descending colon-double lumen ostomy (MDCDLO) in the treatment of high and intermediate types of anorectal malformations.

Methods

We retrospectively reviewed the data of patients who underwent MDCDLO for high or intermediate types of ARMs between June 2016 and December 2021 in our hospital. The basic characteristics were recorded. All patients were followed up monthly to determine if any complication happen.

Results

There were 17 boys and 6 girls diagnosed with high or intermediate types of ARMs in our hospital between June 2016 and December 2021. All 23 patients were cured without complications such as abdominal incision infection, stoma stenosis, incisional hernia, and urinary tract infection in the postoperative follow-up time of 6 months to 6 years except one case of proximal intestinal prolapse was restored under anesthesia.

Conclusion

MDCDLO offers the advantages of simplicity, efficiency, safety, mild trauma, and small scarring in the treatment of high and intermediate types of anorectal malformations.
Occupational status and chronic respiratory diseases: a cross-sectional study based on the data of the Rafsanjan Cohort Study
Authors: Bagheri-Hosseinabadi Zahra , Bahreyni Ali , Basirat Hosein , Khalili Parvin , Vakilian Alireza , Amin Fatemeh
Published: March 2024

Background

The aim of the present study was to investigate the possible connection between occupational status and chronic respiratory diseases (CRDs) among the Iranian population.

Methods

The present cross-sectional study was conducted on 9934 individuals aged 35–70 years enrolled in the Rafsanjan Cohort Study (RCS), a component of the Prospective Epidemiological Research Studies in Iran (PERSIAN). Detailed questionnaires were used to collect information on various factors, such as occupation, sociodemographic characteristics, medical history, anthropometric measurements, physical activity, cigarette and hookah smoking, opium use, and alcohol consumption. The association between occupational class and CRD was evaluated using logistic regression models for rare events.

Results

In the present study, 4624 (46.55%) participants were male, and 5310 (53.45%) were female. The prevalence of CRD among all participants was 2.61%. Occupational activities were classified into two categories: In class I, the largest group was the homemaker and unemployment category (41.73%), followed by self-employment (34.39%), employment (13.03%), and retired individuals (10.84%). In class II, there were pistachio farmers (12.61%), copper miners (3.62%), and others in various occupations (83.76%). Subjects with CRD were significantly more likely to be homemakers, unemployed, elderly, female, less educated, and obese. There was no significant relationship between CRD and job type/occupational status after adjusting for some potential confounding variables.

Conclusions

There was no significant relationship between CRD and job type/occupational status. However, longitudinal studies are needed to assess the impact of job type/occupational status on the risk of CRD.
Deficient gait function despite effect index of the Western Ontario and McMaster university osteoarthritis index score considered cured one year after bilateral total knee arthroplasty
Authors: Zhao Ruipeng , Wei Xiaochun , Hu Shuai , Zhang Yixuan , Wu Hongru , Li Pengcui , Zhao Yu
Published: March 2024

Background

To clarify the value of gait analysis and its consistency with traditional scoring scales for the evaluation of knee joint function after total knee arthroplasty (TKA).

Methods

This study included 25 patients with knee osteoarthritis (KOA) who underwent bilateral TKA, and 25 conditionally matched healthy individuals, categorised into the experimental and control groups, respectively. Patients in the experimental group underwent gait analysis and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) evaluation before and 1 year after TKA. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Pearson’s correlation analysis was performed on the gait and WOMAC score data of the experimental group before and after TKA.

Results

One year after TKA, patients’ gait indices (except gait cycle) were significantly better than before surgery, but significantly worse than that of the control group (P < 0.01). The shape of patients’ plantar pressure curves did not return to normal. Additionally, the discrete trend of related gait indicators reflecting weight-bearing balance and walking stability were smaller than before TKA, but still greater than that of the control group. The WOMAC scores of patients 1 year after TKA were significantly lower than those before TKA (P < 0.001), and the efficacy index was > 80%. The WOMAC scores and gait analysis results were significantly correlated before TKA (P < 0.05).

Conclusions

Gait analysis should be used in conjunction with scoring scales to assess joint functions.
Clinical and radiologic outcomes in patients with meniscal root tears
Authors: Manatrakul Rawee , Loeffler Maximilian , Bharadwaj Upasana U. , Joseph Gabby B. , Lansdown Drew , Feeley Brian , Baal Joe D. , Guimaraes Julio B. , Link Thomas M.
Published: March 2024

Background

Meniscal root tears can lead to early knee osteoarthritis and pain. This study aimed (1) to compare clinical and radiological outcomes between patients who underwent arthroscopic meniscal root repair after meniscal root tears and those who received non-surgical treatment, and (2) to identify whether baseline MRI findings could be potential predictors for future treatment strategies.

Methods

Patients with meniscal root tears were identified from our picture archiving and communication system from 2016 to 2020. Two radiologists reviewed radiographs and MRI studies using Kellgren-Lawrence (KL) grading and a modified Whole Organ MRI Scoring (WORMS) at baseline and follow-up. The median (interquartile range [IQR]) of follow-up radiographs and MRI studies were 134 (44–443) days and 502 (260–1176) days, respectively. MR images were assessed for root tear-related findings. Pain scores using visual analogue scale (VAS) and management strategies (non-surgical vs. arthroscopic root repair) were also collected. Chi-squared tests and independent t-tests were used to assess differences regarding clinical and imaging variables between treatment groups. Logistic regression analyses were performed to evaluate the associations between baseline MRI findings and each future treatment.

Results

Ninety patients were included. VAS pain scores were significantly (p < 0.01) lower after arthroscopic repair compared to conservative treatment (1.27±0.38vs.4±0.52) at the last follow-up visit with median (IQR) of 325 (180–1391) days. Increased meniscal extrusion (mm) was associated with higher odds of receiving non-surgical treatment (OR = 1.65, 95%CI 1.02–2.69,p = 0.04). The odds of having arthroscopic repair increased by 19% for every 1 mm increase in the distance of the tear from the root attachment (OR = 1.19, 95% CI: 1.05–1.36,p < 0.01). The odds of undergoing arthroscopic repair were reduced by 49% for every 1 mm increase in the extent of meniscal extrusion (OR = 0.51, 95% CI: 0.29–0.91,p = 0.02) as observed in the baseline MRI.

Conclusions

Patients who underwent arthroscopic repair had lower pain scores than patients with conservative treatment in the follow-up. Distance of the torn meniscus to the root attachment and the extent of meniscal extrusion were significant predictors for arthroscopic repair in the next three weeks (time from the baseline MRI to the surgery date).
Diagnostic and therapeutic approach to abdominal masses in a country with limited resources
Authors: Adama Saïdou , Balaraba Mohamed Lamine Abani Aichatou , Aliou Zabeirou Oudou , Daouda Bako Inoussa , Kadi Ide , Hama Younssa , Lassey James Didier , Rachid Sani
Published: March 2024

Objective

To report the diagnostic and therapeutic approach for the management of abdominal masses in the General Surgery department of the Niamey General Reference Hospital (HGR).

Materials and methods

This were a retrospective and preliminary study of 2 years and 3 months on patients operated for abdominal masses in the General Surgery department of the HGR. A palpable mass and/or its size on imaging (40 mm) were the inclusion criteria.

Results

Abdominal masses accounted for 6.7% (n = 53) of other pathologies. The average age of the patients was 41.26 years, with a standard deviation of 14.2 and a female predominance of 75.5% (n = 40) with a sex ratio of 0.32. The abdominal mass was clinically palpable in 75.5% (n = 40). Abdominal pelvic ultrasound was performed as a first step in all patients and in 75.5% (n = 40) it specified the origin of the mass. Contrast-enhanced abdomino-pelvic CT scan, performed in 52.8% of patients (n = 28) and in 89.3% (n = 25) specified the preoperative diagnosis. The most frequent etiologies were uterine fibroids, 35.8% (n = 19). In 5.6% (n = 3) the diagnosis was not precise preoperatively despite the two imaging studies, and these patients had underwent exploratory laparotomy. Surgery was the initial therapeutic approach for all patients, and laparoscopy accounted for 22.6% (n = 12). Postoperative complications occurred in 7.5% (n = 11). The death rate was 5.6% of cases (n = 3).

Conclusion

Imaging remains important in the etiological research for abdominal masses. Definitive treatment remains surgical; mortality would be linked to the malignant nature and the significant volume of the mass.
Adsorption of Hg2+/Cr6+ by metal-binding proteins heterologously expressed in Escherichia coli
Authors: Hu Shuting , Wei Zixiang , Liu Teng , Zuo Xinyu , Jia Xiaoqiang
Published: March 2024

Background

Removal of heavy metals from water and soil is a pressing challenge in environmental engineering, and biosorption by microorganisms is considered as one of the most cost-effective methods. In this study, the metal-binding proteins MerR and ChrB derived from Cupriavidus metallidurans were separately expressed in Escherichia coli BL21 to construct adsorption strains. To improve the adsorption performance, surface display and codon optimization were carried out.

Results

In this study, we constructed 24 adsorption engineering strains for Hg2+ and Cr6+, utilizing different strategies. Among these engineering strains, the M’-002 and B-008 had the strongest heavy metal ion absorption ability. The M’-002 used the flexible linker and INPN to display the merRopt at the surface of the E. coli BL21, whose maximal adsorption capacity reached 658.40 μmol/g cell dry weight under concentrations of 300 μM Hg2+. And the B-008 overexpressed the chrB in the intracellular, its maximal capacity was 46.84 μmol/g cell dry weight under concentrations 500 μM Cr6+. While in the case of mixed ions solution (including Pb2+, Cd2+, Cr6+ and Hg2+), the total amount of ions adsorbed by M’-002 and B-008 showed an increase of up to 1.14- and 4.09-folds, compared to the capacities in the single ion solution.

Conclusion

The construction and optimization of heavy metal adsorption strains were carried out in this work. A comparison of the adsorption behavior between single bacteria and mixed bacteria systems was investigated in both a single ion and a mixed ion environment. The Hg2+ absorption capacity is reached the highest reported to date with the engineered strain M’-002, which displayed the merRopt at the surface of chassis cell, indicating the strain’s potential for its application in practical environments.
The roles of French community pharmacists in palliative home care
Authors: Cuchet Isabelle , Dambrun Michael , Bedhomme Sabrina , Savanovitch Chantal , Roussel Hélène Vaillant , Maneval Axelle
Published: March 2024

Background

The World Health Organization identifies pharmacists as a key resource in palliative care. However, the roles of these professionals in end-of-life care at home remain poorly understood, and community pharmacists themselves sometimes struggle to recognize their true role in this care. The aim of our study was to analyze community pharmacists’ representations of their roles in palliative care at home in France.

Methods

The methodology was qualitative and based on semi-structured interviews with community pharmacists (n = 26). The analysis of the interviews was carried out using a qualitative content approach with thematic and lexical analysis.

Results

Three main elements of the community pharmacist’s role were identified: drug expertise, care management, and psychosocial support for patients and their families.

Conclusions

This study highlights a wide variety of roles adopted by French community pharmacists in palliative care at home. Some of these roles, which are in line with WHO recommendations on palliative care, have been little described to date. These roles of community pharmacists in home-based palliative care could be better recognized, and the players better integrated into end-of-life care systems at home, in order to improve such care.

Trial registration

This work was carried out within the framework of a call for projects from the Fondation de France and has received the approval of the University Clermont Auvergne Research Ethics Committee (no. IRB00011540-2021-60).
In vivo antimalarial effect of 1-hydroxy-5,6,7-trimethoxyxanthone isolated from Mammea siamensis T. Anders. flowers: pharmacokinetic and acute toxicity studies
Authors: Chaniad Prapaporn , Chukaew Arnon , Na-ek Prasit , Yusakul Gorawit , Chuaboon Litavadee , Phuwajaroanpong Arisara , Plirat Walaiporn , Konyanee Atthaphon , Septama Abdi Wira , Punsawad Chuchard
Published: March 2024

Background

The potent antiplasmodial activity of 1-hydroxy-5,6,7-trimethoxyxanthone (HTX), isolated from Mammea siamensis T. Anders. flowers, has previously been demonstrated in vitro. However, its in vivo activity has not been reported. Therefore, this study aimed to investigate the antimalarial activity and acute toxicity of HTX in a mouse model and to evaluate the pharmacokinetic profile of HTX following a single intraperitoneal administration.

Methods

The in vivo antimalarial activity of HTX was evaluated using a 4-day suppressive test. Mice were intraperitoneally injected with Plasmodium berghei ANKA strain and given HTX daily for 4 days. To detect acute toxicity, mice received a single dose of HTX and were observed for 14 days. Additionally, the biochemical parameters of the liver and kidney functions as well as the histopathology of liver and kidney tissues were examined. HTX pharmacokinetics after intraperitoneal administration was also investigated in a mouse model. Liquid chromatography triple quadrupole mass spectrometry was used to quantify plasma HTX and calculate pharmacokinetic parameters with the PKSolver software.

Results

HTX at 10 mg/kg body weight significantly suppressed parasitemia in malaria-infected mice by 74.26%. Mice treated with 3 mg/kg HTX showed 46.88% suppression, whereas mice treated with 1 mg/kg displayed 34.56% suppression. Additionally, no symptoms of acute toxicity were observed in the HTX-treated groups. There were no significant alterations in the biochemical parameters of the liver and kidney functions and no histological changes in liver or kidney tissues. Following intraperitoneal HTX administration, the pharmacokinetic profile exhibited a maximum concentration (Cmax) of 94.02 ng/mL, time to attain Cmax (Tmax) of 0.5 h, mean resident time of 14.80 h, and elimination half-life of 13.88 h.

Conclusions

HTX has in vivo antimalarial properties against P. berghei infection. Acute toxicity studies of HTX did not show behavioral changes or mortality. The median lethal dose was greater than 50 mg/kg body weight. Pharmacokinetic studies showed that HTX has a long elimination half-life; hence, shortening the duration of malaria treatment may be required to minimize toxicity.
A QALY is [still] a QALY is [still] a QALY?
Authors: Mahdiani Hamideh , Münch Nikolai , Paul Norbert W.
Published: March 2024

Despite clinical evidence of drug superiority, therapeutic modalities, like combination immunotherapy, are mostly considered cost-ineffective due to their high costs per life year(s) gained. This paper, taking an ethical stand, reevaluates the standard cost-effectiveness analysis with that of the more recent justice-enhanced methods and concludes by pointing out the shortcomings of the current methodologies.
Porcine ear necrosis is associated with social behaviours in weaned piglets
Authors: Boulbria Gwenaël , Nicolazo Théo , Teixeira-Costa Charlotte , Clouard Caroline , Lebret Arnaud , Normand Valérie , Chevance Céline , Jeusselin Justine , Merlot Élodie
Published: March 2024

Background

Porcine ear necrosis (PEN) is a worldwide health issue and its aetiology is still unclear. The aim of this study was to describe the prevalence and the severity of PEN in a commercial farm, associated with pig behaviour and health biomarkers measures.

On two consecutive batches, PEN prevalence was determined at the pen level. PEN scores, blood haptoglobin concentration and oxidative status were measured on two pigs per pen (n = 48 pens) 9, 30 and 50 days (D) after arrival to the post-weaning unit. Social nosing, oral manipulation and aggression of pen mates and exploration of enrichment materials were observed on two to three pigs per pen twice a week from D9 to D50.

Results

At the pen level, the higher the time spent nosing pen mates, the lower the percentage of pigs affected by PEN during both the early and the late post-weaning periods (P < 0.002) and, in the opposite, the higher the time spent orally manipulating pen mates during the late post-weaning period, the higher the percentage of affected pigs (P = 0.03). At the pig level, the higher the increase in hydroperoxides and haptoglobin during the early post-weaning period, the higher the PEN scores on D30 (P < 0.001).

Conclusions

This study suggests that a high incidence of social nosing, which can be an indicator of good social cohesion in a group, was significantly associated with less frequent lesions of PEN. In opposite, high incidence of oral manipulation of pen mates may increase the percentage of PEN-affected pigs. According to these observations, PEN is a multifactorial condition which may have social causes among others.
The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review
Authors: Damiani A , Orlandi M , Bruni C , Bandini G , Lepri G , Scaletti C , Ravaglia C , Frassanito F , Guiducci S , Moggi-Pignone A , Matucci-Cerinic M , Poletti V , Tofani L , Colby TV , Randone S Bellando , Tomassetti Sara
Published: March 2024

Background

The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR).

Methods

PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported.

Results

We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30–100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns.

Conclusions

The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.
An international phase II trial and immune profiling of SBRT and atezolizumab in advanced pretreated colorectal cancer
Authors: Levy Antonin , Morel Daphné , Texier Matthieu , Sun Roger , Durand-Labrunie Jerome , Rodriguez-Ruiz Maria E , Racadot Severine , Supiot Stéphane , Magné Nicolas , Cyrille Stacy , Louvel Guillaume , Massard Christophe , Verlingue Loic , Bouquet Fanny , Bustillos Alberto , Bouarroudj Lisa , Quevrin Clément , Clémenson Céline , Mondini Michele , Meziani Lydia , Tselikas Lambros , Bahleda Rastilav , Hollebecque Antoine , Deutsch Eric
Published: March 2024

Background

Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the colorectal (CRC) cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in advanced cancer patients.

Methods

Eligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint). SBRT was delivered to at least one tumor site, with at least one additional measurable lesion being kept from the radiation field. The primary efficacy endpoint was one-year progression-free survival (PFS) rate from the start of atezolizumab. Sequential tumor biopsies were collected for deep multi-feature immune profiling.

Results

Sixty pretreated (median of 2 prior lines) advanced CRC patients (38 men [63%]; median age, 59 years [range, 20–81 years]; 77% with liver metastases) were enrolled in five centers (France: n = 4, Spain: n = 1) from 11/2016 to 04/2019. All but one (98%) received atezolizumab and 54/60 (90%) received SBRT. The most frequently irradiated site was lung (n = 30/54; 56.3%). Treatment-related G3 (no G4-5) toxicity was observed in 3 (5%) patients. Median OS and PFS were respectively 8.4 [95%CI:5.9–11.6] and 1.4 months [95%CI:1.2–2.6], including five (9%) patients with PFS > 1 year (median time to progression: 19.2 months, including 2/5 MMR-proficient). Best overall responses consisted of stable disease (n = 38; 64%), partial (n = 3; 5%) and complete response (n = 1; 2%). Immune-centric multiplex IHC and RNAseq showed that SBRT redirected immune cells towards tumor lesions, even in the case of radio-induced lymphopenia. Baseline tumor PD-L1 and IRF1 nuclear expression (both in CD3 + T cells and in CD68 + cells) were higher in responding patients. Upregulation of genes that encode for proteins known to increase T and B cell trafficking to tumors (CCL19, CXCL9), migration (MACF1) and tumor cell killing (GZMB) correlated with responses.

Conclusions

This study provides new data on the feasibility, efficacy, and immune context of tumors that may help identifying advanced CRC patients most likely to respond to immuno-radiotherapy.

Trial registration

EudraCT N°: 2015–005464-42; Clinicaltrial.gov number: NCT02992912.
Tumor-derived miR-6794-5p enhances cancer growth by promoting M2 macrophage polarization
Authors: Choi Jae Yeon , Seok Hyun Jeong , Lee Dong Hyeon , Lee Eunju , Kim Tae-Jin , Bae Sangwoo , Shin Incheol , Bae In Hwa
Published: March 2024

Background

Solid tumors promote tumor malignancy through interaction with the tumor microenvironment, resulting in difficulties in tumor treatment. Therefore, it is necessary to understand the communication between cells in the tumor and the surrounding microenvironment. Our previous study revealed the cancer malignancy mechanism of Bcl-w overexpressed in solid tumors, but no study was conducted on its relationship with immune cells in the tumor microenvironment. In this study, we sought to discover key factors in exosomes secreted from tumors overexpressing Bcl-w and analyze the interaction with the surrounding tumor microenvironment to identify the causes of tumor malignancy.

Methods

To analyze factors affecting the tumor microenvironment, a miRNA array was performed using exosomes derived from cancer cells overexpressing Bcl-w. The discovered miRNA, miR-6794-5p, was overexpressed and the tumorigenicity mechanism was confirmed using qRT-PCR, Western blot, invasion, wound healing, and sphere formation ability analysis. In addition, luciferase activity and Ago2-RNA immunoprecipitation assays were used to study the mechanism between miR-6794-5p and its target gene SOCS1. To confirm the interaction between macrophages and tumor-derived miR-6794-5p, co-culture was performed using conditioned media. Additionally, immunohistochemical (IHC) staining and flow cytometry were performed to analyze macrophages in the tumor tissues of experimental animals.

Results

MiR-6794-5p, which is highly expressed in exosomes secreted from Bcl-w-overexpressing cells, was selected, and it was shown that the overexpression of miR-6794-5p increased migratory ability, invasiveness, and stemness maintenance by suppressing the expression of the tumor suppressor SOCS1. Additionally, tumor-derived miR-6794-5p was delivered to THP-1-derived macrophages and induced M2 polarization by activating the JAK1/STAT3 pathway. Moreover, IL-10 secreted from M2 macrophages increased tumorigenicity by creating an immunosuppressive environment. The in vitro results were reconfirmed by confirming an increase in M2 macrophages and a decrease in M1 macrophages and CD8+ T cells when overexpressing miR-6794-5p in an animal model.

Conclusions

In this study, we identified changes in the tumor microenvironment caused by miR-6794-5p. Our study indicates that tumor-derived miR-6794-5p promotes tumor aggressiveness by inducing an immunosuppressive environment through interaction with macrophage.
An integrated metabo-lipidomics profile of induced sputum for the identification of novel biomarkers in the differential diagnosis of asthma and COPD
Authors: Correnti Serena , Preianò Mariaimmacolata , Gamboni Fabia , Stephenson Daniel , Pelaia Corrado , Pelaia Girolamo , Savino Rocco , D’Alessandro Angelo , Terracciano Rosa
Published: March 2024

Background

Due to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a challenging task, complicated in such cases also by asthma–COPD overlap syndrome. The distinct immune/inflammatory and structural substrates of COPD and asthma are responsible for significant differences in the responses to standard pharmacologic treatments. Therefore, an accurate diagnosis is of central relevance to assure the appropriate therapeutic intervention in order to achieve safe and effective patient care. Induced sputum (IS) accurately mirrors inflammation in the airways, providing a more direct picture of lung cell metabolism in comparison to those specimen that reflect analytes in the systemic circulation.

Methods

An integrated untargeted metabolomics and lipidomics analysis was performed in IS of asthmatic (n = 15) and COPD (n = 22) patients based on Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and UHPLC–tandem MS (UHPLC-MS/MS). Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to resulting dataset. The analysis of main enriched metabolic pathways and the association of the preliminary metabolites/lipids pattern identified to clinical parameters of asthma/COPD differentiation were explored. Multivariate ROC analysis was performed in order to determine the discriminatory power and the reliability of the putative biomarkers for diagnosis between COPD and asthma.

Results

PLS-DA indicated a clear separation between COPD and asthmatic patients. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, putrescine showed the highest score. A differential IS bio-signature of 22 metabolites and lipids was found, which showed statistically significant variations between asthma and COPD. Of these 22 compounds, 18 were decreased and 4 increased in COPD compared to asthmatic patients. The IS levels of Phosphatidylethanolamine (PE) (34:1), Phosphatidylglycerol (PG) (18:1;18:2) and spermine were significantly higher in asthmatic subjects compared to COPD.

Conclusions

This is the first pilot study to analyse the IS metabolomics/lipidomics signatures relevant in discriminating asthma vs COPD. The role of polyamines, of 6-Hydroxykynurenic acid and of d-rhamnose as well as of other important players related to the alteration of glycerophospholipid, aminoacid/biotin and energy metabolism provided the construction of a diagnostic model that, if validated on a larger prospective cohort, might be used to rapidly and accurately discriminate asthma from COPD.

Graphical Abstract
“You cannot stay with one person once you begin having sex at a young age”: the prevalence, correlates and effects of early sexual debut among children in Ghana
Authors: Kyei-Arthur Frank , Agyekum Martin Wiredu , Kyei-Gyamfi Sylvester
Published: March 2024

Background

Children’s initiation of early sex has several negative implications on their sexual and reproductive health, growth and development. In Ghana, few studies on early sexual debut have focused on adolescents. Therefore, this study examined the prevalence, causes, correlates and effects of early sexual debut among children aged 8 to 17 in Ghana using secondary data from the Department of Children of the Ministry of Gender, Children, and Social Protection.

Methods

A convergent parallel mixed-method approach guided the study. Descriptive statistics and multivariable binary logistic regression were used to analyse the quantitative data, while thematic analysis was used to analyse the qualitative data.

Results

The study found that the prevalence of early sexual debut among children was 13.2%, which is more predominant among female children. The main causes of early sexual debut include engaging in sex after watching pornography, self-desire to have sex, and being influenced by alcohol consumption. Also, age, sex, education, marital status, religion, ecological zone, living arrangements, and access to the Internet were significant correlates of early sexual debut. Early sexual debut increases children’s risk of unwanted pregnancy, which leads to the termination of children’s education or induced abortion. Also, early sexual debut had adverse impacts on the wellbeing of pregnant children and increased children’s risk of multiple lifetime sexual partners.

Conclusions

This study demonstrated that socio-demographic characteristics of children (e.g., age, sex, education, and marital status) were significant correlates of early sexual debut. Policymakers need to design appropriate interventions, considering the socio-demographic characteristics of children, to curb its occurrence in Ghana.
Hemorrhagic pericardial tamponade in a hemodialysis patient with catheter-related superior vena cava syndrome: a case report
Authors: Zhao Xiaohong , Wang Kang
Published: March 2024

Background

Iatrogenic complications of endovascular treatment for central venous stenosis have not yet been reported. Here we present a case of a patient on maintenance hemodialysis who developed catheter-related superior vena cava syndrome and subsequently suffered from hemorrhagic pericardial tamponade after undergoing percutaneous transluminal angioplasty and stenting.

Case presentation

A 72-year-old male patient presented with uremia, and had been receiving maintenance hemodialysis for the past five years. The patient initially presented with dysfunction of the dialysis catheter (a cuffed tunneled double-lumen catheter in the right internal jugular vein). Imaging examination revealed a segmental occlusion of the superior vena cava stretching from the distal end of the dialysis catheter up to right atrium entrance, apparent compensatory dilatation of the azygos vein, and abundant subcutaneous collaterals. The patient underwent percutaneous transluminal balloon dilatation and stenting (covered stent) of the superior vena cava in the Cath Lab. During the procedure, with forceful advancement of the guidewire, it was observed to progress for a distance before a “smoke” appeared, and an outward spillage of contrast agent was visible, which suggested a possible vessel puncture leading into the mediastinum. Unfortunately, postoperative hemorrhagic pericardial tamponade occurred and the patient developed cardiogenic shock. He experienced symptoms included chest tightness and breath shortness with a recorded blood pressure of 84/60mmHg. After draining 600 ml of bloody fluid through pericardiocentesis, the patient’s symptoms alleviated and his condition improved.

Conclusions

The case emphasizes the need for increased attention to iatrogenic endovascular injuries during catheter placement and endovascular treatment, such as causing pericardial hemorrhage leading to cardiac tamponade.
Combined impact of alcohol consumption and metabolic syndrome on liver dysfunction in an elderly Chinese population
Authors: Zhao Yanrong , Yuan Xiaoxue , Lin Tianxiang , Yang Qing , Jiang Xuewen , Yang Song , Qiu Yinwei
Published: March 2024

Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction.
Comparison of low-dose maximal-intent versus controlled-tempo resistance training on quality-of-life, functional capacity, and strength in untrained healthy adults: a comparative effectiveness study
Authors: Pearson Liam T. , Fox Kai T. , Keenan Ashleigh , Behm David G. , Stuart Sam , Goodall Stuart , Barry Gill
Published: March 2024

Lack of physical activity is a global issue for adults that can lead to sedentary behaviour and a higher prevalence of health complications and chronic diseases, resulting in reduced quality-of-life (QoL) and functional capacity (FC). A potential strategy to mitigate this inactivity is low-dose resistance training (RT); however, physiological, and psychological responses are limited in evidence. Twenty untrained participants aged 30–60 years old (mean ± SD age 42 ± 7 years, mass 77 ± 13 kg, stature 166 ± 8 cm; 18 females and two males) were recruited and randomly assigned to maximal velocity-intent (MI, n = 10) or controlled-tempo (CT, n = 10) RT according to CONsolidated Standards of Reporting Trials (CONSORT) guidelines. Participants attended one training session per week for 6 weeks, consisting of five sets of five repetitions at 60% of one-repetition maximum (1RM) leg press. The interventions differed only during the concentric phase, with MI group pushing with maximal intent, and CT group pushing in a time-controlled manner (3 s). Outcome measures assessed pre- and post-RT included body mass, body mass index (BMI), strength-to-mass ratio, bipedal balance, 6-minute walk test (6MWT), 30-second sit-to-stand (30s-STS), timed up and go (TUG), and leg press 1RM. Time effects were observed for all demographics and FC-related outcomes, such as identical reductions in mass and BMI (− 2%), improvements in strength-to-mass ratio (25%) leg press 1RM (22%), 6MWT (3%), and 30s-STS (14%), as well as a 9% improvement in both TUG-clockwise and anticlockwise. Results show low-dose once-weekly RT is effective in improving QoL, FC, and strength in untrained healthy adults, regardless of modality. Positive responses from participants suggest an increased likelihood of consistent participation for low-dose once-weekly RT over more intense modalities. Retrospective ClinicalTrials.gov ID (TRN): NCT06107855, 24/10/2023.