bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoplasmic Reticulum Stress Potentiates the Immunosuppressive Microenvironment in Hepatocellular Carcinoma by Promoting the Release of SNHG6-Enriched Small Extracellular Vesicles
Authors: Liu Chengdong , Zhou Xiaohan , Zeng Hanyi , Yu Jiaping , Li Wenwen , Zhang Wanli , Liao Yanxia , Wang Haijian , Liu Li 
Published: June 2024

Abstract
Endoplasmic reticulum (ER) stress leads to hepatocellular carcinoma (HCC) progression. Small extracellular vesicles (sEV) play a crucial role in modulating the tumor microenvironment (TME) by influencing cellular communication and immune responses. However, it is unclear whether ER stress modulates the TME through sEVs. In the current study, we investigated the effects and underlying mechanisms of ER stress on the HCC TME. In vivo and in vitro experiments showed that overactivated ER stress was a salient attribute of the immunosuppressive HCC TME. This was caused by the ATF4-promoted release of small nucleolar RNA host gene 6 (SNHG6)-carrying sEVs, which attenuated T cell-mediated immune responses. Overall, SNHG6 modulated the immunosuppressive TME and aggravated ER stress. Meanwhile, targeting SNHG6 facilitated M1-like macrophage and CD8+ T-cell infiltration and decreased the proportion of M2-like macrophages. In addition, SNHG6 knockdown enhanced anti-PD1 immunotherapeutic efficacy. Moreover, in HCC patients, overexpression of SNHG6 was associated with a lack of response to anti-PD1 therapy and poor prognosis, whereas low SNHG6 expression was associated with improved therapeutic efficacy and prognoses. These data indicate that a correlation exists among ER stress, sEVs, immunosuppressive HCC TME, and immunotherapeutic efficacy. Hence, SNHG6-targeted therapy may represent an effective strategy for patients with HCC.
Prevalence of the generalized anxiety disorder in Tunisia: A study of 707 primary care outpatients
Authors: Ben Thabet Jihene , Turki Mariem , Mezghani Molka , Guermazi Asma , Mâalej Mohamed , Charfi Nada , Maalej Manel 
Published: June 2024

Objective This study examined the prevalence and correlates of generalized anxiety disorder (GAD) among primary care outpatients. Method A multicenter, cross-sectional study was conducted that included 707 primary care outpatients being seen at 20 primary healthcare centers in Tunis and Sfax, Tunisia. The Mini International Neuropsychiatric Interview was used to identify a diagnosis of GAD. The Beck Depression Inventory was used to assess depressive symptom severity, and the Sheehan Disability Scale (SDS) was used to measure functional impairment. Results The prevalence of GAD was 11%. GAD was positively correlated with female gender ( P = .005), family history of psychiatric disorder ( P < .001), personal history of suicide attempt ( P = .019), and depressive symptoms ( P < .001). Based on the SDS, severe to very severe functional limitations were reported at work (56.4%), in social life (60.2%), and family life (73.1%) among GAD patients. Conclusion This study indicated a relatively high prevalence of GAD among primary care patients in Tunisia. Risk factors were also determined that may help to identify these patients. This information may help primary care physicians recognize this diagnosis and provide timely referrals to mental health professionals to prevent complications and maximize quality of life.
Clinical Guidelines for the Treatment of Depressive Disorders I. Definitions Prevalence Health Burden
Authors: Parikh Sagar V , Lam Raymond W ,   the CANMAT Depression Work Group
Published: June 2024

Background: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. Methods: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section on "Definitions, Prevalence, and Health Burden” was 1 of 7 articles drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. Results: The 1-year prevalence rate of major depressive disorder (MDD) in Canada is 3.2% to 4.6%, similar to the rates in other countries. MDD frequently runs a chronic or recurrent course and carries high risks for mortality and morbidity. The significant economic costs and disability associated with depressive illness are reduced by effective treatment. Conclusions: MDD is a prevalent medical condition that results in a significant health burden in the world. Vigorous efforts to improve diagnosis, treatment, and prevention are indicated to reduce the societal and personal costs of depressive disorders.
Role of bone single photon emission computed tomography/computed tomography in managing chronic fracture-related infections: Determining the depth of infection and avoiding unnecessary bone procedures
Authors: Lee Seung Hoo , Kim Min Bom , Jeon Yeong June 
Published: June 2024

Purpose Fracture-related infections (FRIs) encompass a broad range of infections associated with bone fractures; they remain a significant clinical challenge. Here, we aimed to investigate the viability of focusing on soft-tissue management in patients suspected of chronic FRI, who exhibit no significant bony uptake on bone single photon emission computed tomography (SPECT)/computed tomography (CT) scans. Methods Between January 2016 and January 2022, we managed 25 patients with chronic FRI or post-traumatic osteomyelitis using technetium 99m-methyl diphosphonate bone SPECT/CT to assess infection depth. Among them, 13 patients showing negligible bony uptake were included and categorized into two groups based on wound discharge reaching the bone/implant (Criteria 1, n = 6) or not (Criteria 2, n = 7). Results Patients in the Criteria 1 group were treated with antibiotics and soft tissue debridement without bony procedure. The average duration of antibiotic therapy was 6.7 weeks. Treatments were individualized, including implant changes, local flaps, skin grafts, and negative pressure wound therapy. No recurrence was reported in the mean follow-up of 21.3 months. Patients in the Criteria 2 group were treated with oral antibiotics (mean duration: 5.9 weeks) and daily wound dressings. No recurrence was reported in the mean follow-up of 26.0 months, and no surgical interventions were required. Conclusion This study demonstrates the feasibility of focusing on soft-tissue management in patients with chronic FRI showing minimal bony uptake on bone SPECT/CT. Our treatment protocol avoided unnecessary surgical bone procedures, resulting in successful clinical outcomes with no recurrences.
Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats
Authors: Bhatt Laxit K. , Shah Chitrang R. , Patel Jitendra H. , Rajwadi Viral I. , Dwivedi Pankaj , Patel Rajesh J. , Ranvir Ramchandra K. , Patel Harilal , Sundar Rajesh , Jain Mukul R. 
Published: June 2024

These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2/15) at the highest dose (15 mg/kg/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15 mg/kg/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165 mg/kg/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7 mg/kg/day in female rats and 15 mg/kg/day in male rats.
Effectiveness of interventions to prevent abuse in people living with dementia in community settings: A systematic review
Authors: Peter A Seelia , Prabhu M Mukhyaprana , Tolson Debbie , Nayak Baby S , Bhandary Rajeshkrishna P , V Binil , Devi Elsa Sanatombi 
Published: June 2024

The abuse of older adults is a societal, and legal issue. A person living with dementia is at high risk for abuse due to their physical and cognitive decline. Objectives This review examined the evidence for interventions to prevent the abuse of people living with dementia in the community. Methods The articles were retrieved from 2000 to 2023 from six databases, including MEDLINE via PubMed, CINAHL Plus via EBSCO, EMBASE, ProQuest Medical Library, Web of Science, and Scopus. The research articles that focused on finding the effectiveness of interventions for preventing abuse of people living with dementia in community settings were included in this review. The review included randomized controlled trials and pre-test post-test trials only. The quality appraisal of the eligible studies was done using ROB 2 and ROBINS II. The findings were tabulated and narratively synthesised. Results Out of 1831 articles, only three were included in this review. Only two RCTs were included in this efficacy review. Both the studies showed that the interventions were not effective in reducing abuse. The studies utilised family caregiver interventions like psychological interventions and online supportive education. The review identified psychological interventions with some evidence. Another study was a quasi-experimental study that used dialectical behaviour therapy as an intervention to reduce abuse occurrence. The study showed low evidence and focused only on reporting of elder abuse as an outcome. Conclusion This review found very few studies and was not able to draw a conclusion on the effectiveness of interventions for abuse in people living with dementia. Given the paucity of research, there is a clear need to identify how to overcome the challenges faced in elder abuse research and further refine the development of approaches to reduce elder abuse among people living with dementia in community settings.
First multicenter study evaluating the utility of the BENCHMARKTM BMXTM 81 large-bore access catheter in neurovascular interventions
Authors: Abdelsalam Ahmed , Fountain Hayes B , Ramsay Ian A , Luther Evan M , Sowlat Mohammad Mahdi , Silva Michael A , Hassan Ameer E , Patel Aman B , Eatz Tiffany , Joseph Pradeep , Regenhardt Robert W , Satti Sudhakar R , Siddiqui Adnan H , Sanikommu Sai , Baig Ammad A , Khandelwal Priyank , Spiotta Alejandro M , Starke Robert M 
Published: June 2024

Introduction This study is the first multicentric report on the safety, efficacy, and technical performance of utilizing a large bore (0.081″ inner diameter) access catheter in neurovascular interventions. Methods Data were retrospectively collected from seven sites in the United States for neurovascular procedures via large bore 0.081″ inner diameter access catheter (Benchmark BMX81, Penumbra, Inc.). The primary outcome was technical success, defined as the access catheter reaching its target vessel. Safety outcomes included periprocedural device-related and access site complications. Results There were 90 consecutive patients included. The median age of the patients was 63 years (IQR: 53, 68); 53% were female. The most common interventions were aneurysm embolization (33.3%), carotid stenting (12.2%), and arteriovenous malformation embolization (11.1%). The transradial approach was most used (56.7%), followed by transfemoral (41.1%). Challenging anatomic variations included severe vessel tortuosity (8/90, 8.9%), type 2 aortic arch (7/90, 7.8%), type 3 aortic arch (2/90, 2.2%), bovine arch (2/90, 2.2%), and severe angle (<30°) between the subclavian artery and target vessel (1/90, 1.1%). Technical success was achieved in 98.9% of the cases (89/90), with six cases requiring a switch from radial to femoral (6.7%) and one case from femoral to radial (1.1%). There were no access site complications or complications related to the 0.081″ catheter. Two postprocedural complications occurred (2.2%), unrelated to the access catheter. Conclusion The BMX™ 81 large-bore access catheters was safe and effective in both radial and femoral access across a wide range of neurovascular procedures, achieving high technical success without any access site or device-related complications.
Enhanced diaphragm excursion and exercise tolerance in COPD patients through inspiratory muscle training after standardised pulmonary rehabilitation: randomised controlled trial
Authors: Shiraishi Masashi , Higashimoto Yuji , Sugiya Ryuji , Mizusawa Hiroki , Takeda Yu , Noguchi Masaya , Nishiyama Osamu , Yamazaki Ryo , Kudo Shintarou , Kimura Tamotsu , Matsumoto Hisako 
Published: June 2024

ObjectiveInspiratory muscle training (IMT) is used to improve inspiratory muscle strength in patients with COPD. However, the effect of IMT on diaphragmatic function has not yet been thoroughly evaluated. This study aimed to evaluate the effect of IMT on maximum diaphragmatic excursion (DEmax) using ultrasonography in patients with COPD.MethodsThis was a single-centre, randomised, prospective, parallel-group, unblinded controlled trial involving 38 participants with stable COPD. Participants underwent a standardised 12-week pulmonary rehabilitation (PR) programme followed by a 12-week IMT programme, consisting of home-based IMT and low-frequency outpatient PR sessions supervised by physiotherapists (once every 2 weeks),versuslow-frequency outpatient PR alone as a control. The DEmaxand exercise tolerance were measured.ResultsOut of the 38 patients initially enrolled in the PR programme, 33 successfully completed it and were subsequently randomised to the IMT programme. Finally, 15 (94%) and 14 (88%) patients from the IMT and control groups, respectively, completed the study. Following the IMT programme, DEmaxincreased in the IMT group (mean±sd50.1±7.6 mm to 60.6±8.0 mm, p<0.001), but not in the control group (47.4±7.9 mm to 46.9±8.3 mm, p=0.10). Changes in DEmaxand exercise tolerance (peak oxygen uptake) were greater in the IMT group than in the control group (both p<0.01).ConclusionsIMT following the PR programme improved DEmaxand exercise tolerance. Therefore, DEmaxmay be an important outcome of IMT.
Efficacy of tezepelumab in patients with severe asthma and persistent airflow obstruction
Authors: Israel Elliot , Castro Mario , Ambrose Christopher S. , Llanos Jean-Pierre , Molfino Nestor A. , Martin Nicole L. , Ponnarambil Sandhia S. , Martin Neil 
Published: June 2024

BackgroundPersistent airflow obstruction (PAO) in patients with asthma can be difficult to treat. Tezepelumab blocks thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis. This analysis evaluated the efficacy of tezepelumab in patients with severe, uncontrolled asthma and PAO.MethodsPATHWAY (phase 2b) and NAVIGATOR (phase 3) were multicentre, randomised, double-blind, placebo-controlled studies. Thispost hocanalysis included PATHWAY and NAVIGATOR patients who received tezepelumab 210 mg or placebo every 4 weeks for 52 weeks. Change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and the annualised asthma exacerbation rate (AAER) over 52 weeks were assessed in patients with and without PAO (post-bronchodilator FEV1/forced vital capacity ratio <0.7) at baseline.ResultsOf the 1334 included patients, 782 (58.6%) had PAO at baseline. At week 52, greater improvements in pre-bronchodilator FEV1from baseline were observed in tezepelumabversusplacebo recipients with PAO (least-squares (LS) mean 0.24versus0.07 L; difference 0.17 L, 95% confidence interval (CI): 0.11–0.23) and without PAO (LS mean 0.20versus0.12 L; difference 0.08 L, 95% CI: 0.01–0.15). Tezepelumab reduced the AAERversusplacebo by 61% (95% CI: 51–69) and 56% (95% CI: 42–67) in patients with and without PAO, respectively. For patients with PAO at baseline, the proportion without PAO at week 52 was higher with tezepelumab (12.1%) than placebo (6.6%) (odds ratio 1.96, 95% CI: 1.30–2.94).ConclusionTezepelumab improved lung function and reduced exacerbationsversusplacebo in patients with severe, uncontrolled asthma with and without PAO.
Biological characteristics and metabolic phenotypes of different anastomosis groups of Rhizoctonia solani strains
Authors: Sun Meili , Wang Hancheng , Ye Guo , Zhang Songbai , Li Zhen , Cai Liuti , Wang Feng 
Published: June 2024

Abstract
Background
Rhizoctonia solani is an important plant pathogen worldwide, and causes serious tobacco target spot in tobacco in the last five years. This research studied the biological characteristics of four different anastomosis groups strains (AG-3, AG-5, AG-6, AG-1-IB) of R. solani from tobacco. Using metabolic phenotype technology analyzed the metabolic phenotype differences of these strains.

Results
The results showed that the suitable temperature for mycelial growth of four anastomosis group strains were from 20 to 30oC, and for sclerotia formation were from 20 to 25oC. Under different lighting conditions, R. solani AG-6 strains produced the most sclerotium, followed by R. solani AG-3, R. solani AG-5 and R. solani AG-1-IB. All strains had strong oligotrophic survivability, and can grow on water agar medium without any nitrutions. They exhibited three types of sclerotia distribution form, including dispersed type (R. solani AG-5 and AG-6), peripheral type (R. solani AG-1-IB), and central type (R. solani AG-3). They all presented different pathogenicities in tobacco leaves, with the most virulent was noted by R. solani AG-6, followed by R. solani AG-5 and AG-1-IB, finally was R. solani AG-3. R. solani AG-1-IB strains firstly present symptom after inoculation. Metabolic fingerprints of four anastomosis groups were different to each other. R. solani AG-3, AG-6, AG-5 and AG-1-IB strains efficiently metabolized 88, 94, 71 and 92 carbon substrates, respectively. Nitrogen substrates of amino acids and peptides were the significant utilization patterns for R. solani AG-3. R. solani AG-3 and AG-6 showed a large range of adaptabilities and were still able to metabolize substrates in the presence of the osmolytes, including up to 8% sodium lactate. Four anastomosis groups all showed active metabolism in environments with pH values from 4 to 6 and exhibited decarboxylase activities.

Conclusions
The biological characteristics of different anastomosis group strains varies, and there were significant differences in the metabolic phenotype characteristics of different anastomosis group strains towards carbon source, nitrogen source, pH, and osmotic pressure.
Developing survey weights to ensure representativeness in a national, matched cohort study: results from the children and young people with Long Covid (CLoCk) study
Authors: Rojas Natalia K , De Stavola Bianca L , Norris Tom , Cortina-Borja Mario , Nugawela Manjula D , Hargreaves Dougal , Dalrymple Emma , McOwat Kelsey , Simmons Ruth , Stephenson Terence , Shafran Roz ,   CLoCk Consortium, Pereira Snehal M Pinto 
Published: June 2024

Abstract
Background
Findings from studies assessing Long Covid in children and young people (CYP) need to be assessed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and any generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP.

Methods
Logistic regression models were fitted to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall ‘envisioned population’ survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census.

Results
Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example, re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings.

Conclusions
Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.
Comparative safety assessment of nasogastric versus nasojejunal feeding initiated within 48 hours post-admission versus unrestricted timing in moderate or severe acute pancreatitis: a systematic review and meta-analysis
Authors: Wang Ming , Shi Haiyan , Chen Qianqian , Su Binbin , Dong Xiaoyu , Shi Hui , Xu Shiping 
Published: June 2024

Abstract
Background
The primary objective of this study is to comparatively assess the safety of nasogastric (NG) feeding versus nasojejunal (NJ) feeding in patients with acute pancreatitis (AP), with a special focus on the initiation of these feeding methods within the first 48 h of hospital admission.

Methods
Studies were identified through a systematic search in PubMed, EMbase, Cochrane Central Register of Controlled Trials, and Web of Science. Four studies involving 217 patients were included. This systematic review assesses the safety and efficacy of nasogastric versus nasojejunal feeding initiated within 48 h post-admission in moderate/severe acute pancreatitis, with a specific focus on the timing of initiation and patient age as influential factors.

Results
The results showed that the mortality rates were similar between NG and NJ feeding groups (RR 0.86, 95% CI 0.42 to 1.77, P = 0.68). Significant differences were observed in the incidence of diarrhea (RR 2.75, 95% CI 1.21 to 6.25, P = 0.02) and pain (RR 2.91, 95% CI 1.50 to 5.64, P = 0.002) in the NG group. The NG group also showed a higher probability of infection (6.67% vs. 3.33%, P = 0.027) and a higher frequency of multiple organ failures. Subgroup analysis for early intervention (within 48 h) showed a higher risk of diarrhea in the NG group (RR 2.80, P = 0.02). No significant differences were found in the need for surgical intervention, parenteral nutrition, or success rates of feeding procedures.

Conclusion
This meta-analysis highlights the importance of considering the method and timing of nutritional support in acute pancreatitis. While NG feeding within 48 h of admission increases the risk of certain complications such as diarrhea and infection, it does not significantly impact mortality or the need for surgical intervention.