bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymph node ratio is a prospective prognostic indicator for locally advanced gastric cancer patients after neoadjuvant chemotherapy
Authors: Jiang Qi , Zeng Xiangyu , Zhang Chenggang , Yang Ming , Fan Jun , Mao Gan , Shen Qian , Yin Yuping , Liu Weizhen , Tao Kaixiong , Zhang Peng
Published: August 2022

Background

The accuracy of lymph node ratio (LNR) as a prognostic index remains to be proven for gastric cancer patients after neoadjuvant chemotherapy (NACT). This study sought to investigate the prognostic value of LNR in locally advanced gastric cancer (LAGC) patients after NACT.

Methods

LAGC patients with clinical TNM stages 2–3, Her2(−), and Eastern Cooperative Oncology Group, scores 0–2 are routinely scheduled with NACT. Patients with LAGC after NACT and surgical operation between January 2012 and October 2020 were retrospectively reviewed. The correlation between LNR and survival was investigated.

Results

Overall, 148 patients were enrolled: 103 with low-LNR (LNR ≤ 30%) and 45 with high-LNR (LNR > 30%). Approximately, 50.5% and 24.4% patients responded to NACT at the primary site in the low-LNR and high-LNR groups, respectively. The overall survival (OS) and progression-free survival (PFS) of low-LNR group were considerably better than those of high-LNR group (3-year OS: 81.9% vs 18.5%,P< 0.001; 3-year PFS: 72.6% vs 13.5%,P< 0.001). In the low-LNR group, OS and PFS were superior in patients with tumor regression grade (TRG) 0–2 than in those with TRG 3 (3-year OS: 89.2% vs 73.2%,P= 0.086; 3-year PFS: 80.3% vs 66.5%,P= 0.036). In association with OS and PFS, the degree of tumor differentiation, TRG, and LNR were identified as predictive factors, and LNR was identified as the independent prognostic factor in univariate and multivariate analyses, respectively.

Conclusions

LNR is a prospective index of prognosis in patients with LAGC after NACT.
Association between exposure to social media and knowledge of sexual and reproductive health among adolescent girls: evidence from the UDAYA survey in Bihar and Uttar Pradesh, India
Authors: Saha Ria , Paul Pintu , Yaya Sanni , Banke-Thomas Aduragbemi
Published: August 2022

Background

Poor sexual and reproductive health (SRH) outcomes amongst adolescent girls in India have been associated with inadequate knowledge of SRH. Evidence suggests that social media can promote health-seeking behaviors. Our objective in this study was to determine the association between exposure to social media and SRH knowledge among adolescent girls in Bihar and Uttar Pradesh, India.

Methods

A cross-sectional study was conducted with 10,425 adolescent girls from the UDAYA survey (wave-2, 2018–19). Girls’ exposure to social media was the key predictor, and SRH knowledge of sexual intercourse and pregnancy, contraceptive methods, and HIV/AIDS were outcomes of interest. Multivariable logistic regression models were performed to assess the association between exposure to social media and knowledge of SRH among adolescent girls.

Results

Of the study participants (n = 10,425), 28.0% (n = 3,160) had exposure to social media. Overall, 8.7%, 11.4%, and 6.6% of respondents had sufficient knowledge of sexual intercourse and pregnancy, contraceptive methods, and HIV/AIDS, respectively. Exposure to social media was associated with increased odds of knowledge of sexual intercourse and pregnancy (Odds ratio [OR]: 1.38; 95% confidence interval [CI]: 1.18, 1.61), contraceptive methods (OR: 1.46; 95% CI: 1.27, 1.67), and HIV/AIDS (OR: 2.18; 95% CI: 1.84, 2.58).

Conclusions

Our study shows the potency of exposure to social media in influencing SRH knowledge, which exclusively benefits female adolescents who are educated, residing in urban areas, and from wealthier families. Digital media-focused interventions inclusive of socio-cultural contexts (e.g., strategic investment in education and creating economic opportunities) are crucial to optimize social media's impact on SRH knowledge enhancements.
Outcomes and prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy
Authors: Liu Jing , Tang Guyu , Zhou Qin , Kuang Weilu
Published: August 2022

Background

To investigate the prognostic factors affecting long-term survival in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT).

Methods

We retrospectively analyzed 192 naive LACC (stage IIB–IVA) patients who underwent intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy in Xiangya Hospital from January 2014 to June 2017. The clinicopathological factors of all patients were collected. To explore the relationship between factors and prognosis, survival rates were estimated by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to evaluate the effect of various factors on overall survival (OS) and progression-free survival (PFS). The nomogram and calibration curves were generated on the basis of survival analysis.

Results

The median follow-up time was 39.5 months. There-year rates of OS and PFS were 89.1% and 82.8%. LACC patients with non-squamous cell carcinoma [NSCC, including adenocarcinoma or adenosquamous carcinoma (AC/ASC)], advanced stage (IIIA-IVA), initially positive lymph node (pelvic or para-aortic lymph node, PLN/PALN), and a lower pretreatment hemoglobin (HGB) level (< 126 g/L) had lower survival rates. In univariate analysis, patients with NSCC, advanced stage, PLN or PALN metastasis had worse OS. Patients with NSCC, advanced stage, PLN or PALN metastasis, and a lower pretreatment HGB level had worse PFS. In multivariate analysis, NSCC and PALN metastasis were independent prognostic parameters of OS. NSCC, PALN metastasis and a lower pretreatment HGB level were independent prognostic parameters of PFS.

Conclusions

NSCC and PALN metastasis were poor prognostic factors of OS and PFS, a lower pretreatment HGB level was an independent prognostic factor of PFS in LACC patients treated with CCRT.
Effects of steam on polysaccharides from Polygonatum cyrtonema based on saccharide mapping analysis and pharmacological activity assays
Authors: Chen Zherui , Zhu Baojie , Chen Zhixin , Cao Wen , Wang Junqiao , Li Shaoping , Zhao Jing
Published: August 2022

Background

Polygonatum cyrtonema, one of origins of Polygonata Rhizoma (HuangJing in Chinese), is traditionally steamed repeatedly before being used as herbal medicine in China. However, there has no standard for steaming of HuangJing. Therefore, a comprehensive study for effects of steam on polysaccharides from Polygonatum cyrtonema based on saccharide mapping, a powerful method developed for polysaccharides analysis, and pharmacological activity are still necessary, which is helpful to explore the effect of steam on the physiochemical and biological activities of its polysaccharides and develop steaming standard of Polygonatum cyrtonema.

Methods

To explore the effect of steam on physiochemical and biological activities of P. cyrtonema polysaccharides (PCP), six polysaccharides named PCP0, PCP1, PCP2, PCP3, PCP4 and PCP5 were extracted from the herb consecutively steamed for 0–5 times, respectively. Their molecular weight distribution, monosaccharide composition and PACE fingerprints were investigated through HPSEC-MALLS-RID, HPAEC-PAD and saccharide mapping based on polysaccharides analysis by using carbohydrate gel electrophoresis (PACE) and HPTLC, respectively. In addition, their antioxidant ability and immunostimulatory activities on RAW 264.7 cells in terms of NO production and phagocytosis were compared.

Results

Results suggested that molecular weights could be changed during steam, which increased by first steaming and then decreased with further steaming though all polysaccharides’ molecular weights were 105-107 Da. They all showed irregularly spherical conformation in aqueous solution based on AFM imaging. Their monosaccharide composition and PACE fingerprints were significantly different after steaming, i.e., galactose increased while glucose and mannose decreased, and β-1,4-Galp appeared while β-1,4-Manp increased, after steaming. Steamed PCP significantly increased scavenging activity against ABTS radicals, while PCP0 had the best immunostimulatory effect on RAW 264.7 in terms of NO production and phagocytosis.

Conclusions

In summary, steam significantly affected the chemical composition and bioactivities of polysaccharides from P. cyrtonema. Considering the balance beneficial effects of steaming on antioxidant and immunopotentiation activities of PCP, 2 times of continuous steam is the optimal choice under the given conditions.
Transcriptome deregulation of peripheral monocytes and whole blood in GBA-related Parkinson’s disease
Authors: Riboldi Giulietta Maria , Vialle Ricardo A. , Navarro Elisa , Udine Evan , de Paiva Lopes Katia , Humphrey Jack , Allan Amanda , Parks Madison , Henderson Brooklyn , Astudillo Kelly , Argyrou Charalambos , Zhuang Maojuan , Sikder Tamjeed , Oriol Narcis J. , Kumar Shilpa Dilip , Janssen William , Sowa Allison , Comi Giacomo P. , Di Fonzo Alessio , Crary John F. , Frucht Steven J. , Raj Towfique
Published: August 2022

Background

Genetic mutations in beta-glucocerebrosidase (GBA) represent the major genetic risk factor for Parkinson’s disease (PD). GBA participates in both the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated.

Methods

We characterized the transcriptomic profiles of circulating monocytes in a population of patients with PD and healthy controls (CTRL) with and without GBA variants (n = 23 PD/GBA, 13 CTRL/GBA, 56 PD, 66 CTRL) and whole blood (n = 616 PD, 362 CTRL, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy.

Results

We observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, PD/GBA showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing. Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to non-manifesting GBA-carriers, as also observed at the ultrastructural levels. Transcriptomic results were only partially replicated in an independent cohort of whole blood samples, suggesting cell-type specific changes.

Conclusions

Overall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD.
Differentially expression and function of circular RNAs in ovarian cancer stem cells
Authors: Sohn Eun Jung
Published: August 2022

Background

Circular RNAs (circRNAs) are noncoding RNAs that regulate miRNA expression; however, their functions in cancer stem cells (CSCs) are not well known.

Methods

To determine the function of differentially expression of circRNAs associated with ovarian CSCs, circRNA profiling was conducted using a circRNA-based microarray on sphere-forming cells derived from A2780 and SKOV3 epithelial ovarian cancer cells termed A2780-SP and SKOV3-SP compared to monolayer cells such as A2780 and SKOV3 cells, respectively. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the biological functions of the circRNAs expressed in CSCs.

Results

The circRNA-based microarray data showed that 159 circRNAs were significantly upregulated (fold change > 1.5) and 55 circRNAs were downregulated in ovarian CSCs compared to monolayer cells. GO and KEGG enrichment analysis of differentially expressed circRNAs in ovarian CSCs showed that they were mainly involved in cell cycle, histone modification, cellular protein metabolic process, cell cycle, apoptotic signaling pathway, and ubiquitin-mediated proteolysis in ovarian cancer. In addition, the hsa-circRNA000963-miRNA-mRNA regulatory network was constructed based on potential target of miRNAs. These analyses involved that the biological function of the hsa-circRNA00096/miRNA/mRNA network was involved in signaling pathways regulating pluripotency of stem cells, PI3K-Akt signaling pathway, cell cycle, p53 signaling pathway, Wnt signaling pathway, calcium modulating pathway, and production of miRNAs involved in gene silencing by miRNA.

Conclusions

Our data demonstrate the expression profiles of circRNAs in ovarian CSCs and suggest that circRNAs may be potential diagnostic and predictive biomarkers of ovarian cancer.
An increased potential for organ donors may be found among patients with out-of-hospital cardiac arrest
Authors: Rasmussen Mads Anders , Moen Håvard Storsveen , Milling Louise , Munthe Sune , Rosenlund Christina , Poulsen Frantz Rom , Brøchner Anne Craveiro , Mikkelsen Søren
Published: August 2022

Introduction

A prehospital system where obvious futile cases may be terminated prehospitally by physicians may reduce unethical treatment of dying patients. Withholding treatment in futile cases may seem ethically sound but may keep dying patients from becoming organ donors. The objective of this study was to characterise the prehospital patients who underwent organ donation. The aim was to alert prehospital physicians to a potential for an increase in the organ donor pool by considering continued treatment even in some prehospital patients with obvious fatal lesions or illness.

Methods

This is a retrospective register-based study from the Region of Southern Denmark. The prehospital medical records from patients who underwent organ donation after prehospital care from 1st of January 2016–31st of December 2020 were screened for inclusion. The outcome measures were prehospital diagnosis, vital parameters, and critical interventions.

Results

In the five year period, one-hundred-and-fifty-one patients were entered into a donation process in the health region following prehospital care. Sixteen patients were excluded due to limitations in data availability. Of the 135 patients included, 36.3% had a stroke. 36.7% of these patients were intubated prehospitally. 15.6% had subarachnoideal haemorrhage. 66.7% of these were intubated prehospitally. 10.4% suffered from head trauma. 64.3% of these patients were intubated at the scene. In 21.5% of the patients, the prehospitally assigned tentative diagnosis was missing or included a diverse spectrum of medical and surgical emergencies. Twenty-two patients (16.3%) were resuscitated from cardiac arrest. 81.8% were intubated at the scene.

Conclusion

The majority of the patients who became organ donors presented prehospitally with intracranial pathology. However, 30% of the patients that later underwent an organ donation process had other prehospital diagnoses. Among these, one patient in six had out-of-hospital cardiac arrest. Termination of treatment in patients with cardiac arrest is not uncommon in physician-manned prehospital emergency medical systems. An organ donation process cannot be initiated prehospitally but can be shut down if treatment is withheld or terminated. We contend that there is a potential for enlarging the donor pool if the decision processes in out-of-hospital cardiac arrest include considerations concerning future procurement of organ donors.
Diencephalic syndrome in childhood, a challenging cause of failure to thrive: miniseries and literature review
Authors: Trapani Sandra , Bortone Barbara , Bianconi Martina , Rubino Chiara , Sardi Iacopo , Lionetti Paolo , Indolfi Giuseppe
Published: August 2022

The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare but potentially lethal cause of failure to thrive in infancy. Poor weight gain or weight loss, the characteristic presenting feature, often firstly attributed to gastrointestinal or endocrinological or genetic diseases, is secondary to a malfunctioning hypothalamus, caused by a diencephalic tumor. Due to its unexpected clinical onset, diagnostic delay and misdiagnosis are common. We described a case series of 3 children with diencephalic syndrome admitted at our Hospital, over a 5-year period. Furthermore, a narrative review on all pediatric cases published in the last seventy years was performed. Clinical pattern, timing to diagnosis, neuroimaging, management, and outcome were analyzed. Our three cases are singularly described in all clinical and diagnostic findings. Overall, 100 children were selected; all these cases as well as our children presented with failure to thrive: 96% had body mass index or weight-length/height ratio lower than 5th percentile. Vomiting and hyperactivity are reported in 35 and 26% of cases, respectively. The neurological features, mainly nystagmus reported in 43%, may occur late in the disease course. In conclusion, the diagnostic delay is the hallmark of diencephalic syndrome, confirming the lack of knowledge by clinicians. The poor weight gain/loss despite adequate length growth and food intake, especially in children with hyperactivity and good psychomotor development, should alert pediatricians towards this condition, before neurological signs/symptoms occurrence.
Trial Forge Guidance 3: randomised trials and how to recruit and retain individuals from ethnic minority groups—practical guidance to support better practice
Authors: Dawson Shoba , Banister Katie , Biggs Katie , Cotton Seonaidh , Devane Declan , Gardner Heidi , Gillies Katie , Gopalakrishnan Gosala , Isaacs Talia , Khunti Kamlesh , Nichol Alistair , Parker Adwoa , Russell Amy M. , Shepherd Victoria , Shiely Frances , Shorter Gillian , Starling Bella , Williams Hywel , Willis Andrew , Witham Miles D. , Treweek Shaun
Published: August 2022

Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities.

This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations.

We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.
Integration of smoking cessation into standard treatment for patients receiving opioid agonist therapy who are smoking tobacco: protocol for a randomised controlled trial (ATLAS4LAR)
Authors: Druckrey-Fiskaaen Karl Trygve , Furulund Einar , Daltveit Jan Tore , Vold Jørn Henrik , Lid Torgeir Gilje , Madebo Tesfaye , Fadnes Lars Thore ,   for the ATLAS4LAR Study Group, Buljovcic Vibeke Bråthen , Fondenes Trude , Gundersen Per , Carlsen Siv-Elin Leirvåg , Nordbotn Mette Hegland , Pierron Marianne Cook , Sundal Christine , Vold Jørn Henrik , Bergsaker Maren Borsheim , Dahl Eivin , Eielsen Tone Lise , Fiskå Torhild , Holder Eirik , Cruickshank Tine Selmer , Wilk Ewa Joanna
Published: August 2022

Background

About 85% of patients receiving opioid agonist therapy (OAT) for opioid dependence are smoking tobacco. Although smoke-related pulmonary diseases are significant contributors to morbidity and mortality, few smoking cessation interventions are evaluated within this group, and few OAT patients are offered smoking cessation as an integrated part of their addiction treatment. This study protocol describes an integrated smoking cessation intervention aimed at patients receiving OAT and smoking tobacco.

Methods

This is a multicentre, randomised controlled clinical trial that will recruit 266 daily tobacco smoking patients receiving OAT in OAT outpatient clinics in Bergen and Stavanger, Norway. The patients randomised for the intervention arm will be offered smoking cessation therapy consisting of weekly brief behavioural interventions and prescription-free nicotine replacement products. In the control arm, patients will receive standard care without any added interventions related to smoking cessation.

The smoking cessation intervention includes psychoeducational techniques with components from motivational interviewing, and nicotine replacement products such as nicotine lozenges, patches, and chewing gum. The duration of the intervention is 16 weeks, with the option of extending it by a further 8 weeks. The main outcomes are measured at 16 weeks after initiation of the intervention, and sustained effects are evaluated 1 year after intervention initiation.

The primary outcome is smoking cessation verified by carbon monoxide (CO) levels or at least a 50% reduction in the number of cigarettes smoked. Secondary outcomes are changes in psychological well-being, biochemical inflammation markers, changes in physical health, quality of life, and fatigue.

Discussion

Integration of other treatments to standard OAT care improves adherence and completion rates providing another rationale for integrated smoking cessation treatment. Thus, if integrated smoking cessation treatment is superior to standard care, this trial provides important information on further scale-up.

Trial registration

ClinicalTrials.gov NCT05290025. Registered on 22 March 2022
Study protocol of a multiphase optimization strategy trial (MOST) for delivery of smoking cessation treatment in lung cancer screening settings
Authors: Ostroff Jamie S. , Shelley Donna R. , Chichester Lou-Anne , King Jennifer C. , Li Yuelin , Schofield Elizabeth , Ciupek Andrew , Criswell Angela , Acharya Rashmi , Banerjee Smita C. , Elkin Elena B. , Lynch Kathleen , Weiner Bryan J. , Orlow Irene , Martin Chloé M. , Chan Sharon V. , Frederico Victoria , Camille Phillip , Holland Susan , Kenney Jessica
Published: August 2022

Background

There is widespread agreement that the integration of cessation services in lung cancer screening (LCS) is essential for achieving the full benefits of LCS with low-dose computed tomography (LDCT). There is a formidable knowledge gap about how to best design feasible, effective, and scalable cessation services in LCS facilities. A collective of NCI-funded clinical trials addressing this gap is the Smoking Cessation at Lung Examination (SCALE) Collaboration.

Methods

The Cessation and Screening to Save Lives (CASTL) trial seeks to advance knowledge about the reach, effectiveness, and implementation of tobacco treatment in lung cancer screening. We describe the rationale, design, evaluation plan, and interventions tested in this multiphase optimization strategy trial (MOST). A total of 1152 screening-eligible current smokers are being recruited from 18 LCS sites (n= 64/site) in both academic and community settings across the USA. Participants receive enhanced standard care (cessation advice and referral to the national Quitline) and are randomized to receive additional tobacco treatment components (motivational counseling, nicotine replacement patches/lozenges, message framing). The primary outcome is biochemically validated, abstinence at 6 months follow-up. Secondary outcomes are self-reported smoking abstinence, quit attempts, and smoking reduction at 3 and 6 months. Guided by the Implementation Outcomes Framework (IOF), our evaluation includes measurement of implementation processes (reach, fidelity, acceptability, appropriateness, sustainability, and cost).

Conclusion

We will identify effective treatment components for delivery by LCS sites. The findings will guide the assembly of an optimized smoking cessation package that achieves superior cessation outcomes. Future trials can examine the strategies for wider implementation of tobacco treatment in LDCT-LCS sites.

Trial registration

ClinicalTrials.govNCT03315910
The effect of continuing versus withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers on mortality and major adverse cardiovascular events in hypertensive patients undergoing elective non-cardiac surgery: study protocol for a multi-centric open-label randomised controlled trial
Authors: Misra Satyajeet , Parida Satyen , Sahajanandan Raj , Behera Bikram Kishore , Senthilnathan Muthapillai , Mariappan Ramamani , Chandy Tony Thomson ,   For the ACE investigators
Published: August 2022

Background

Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are commonly prescribed to patients with hypertension. These drugs are cardioprotective in addition to their blood pressure-lowering effects. However, it is debatable whether hypertensive patients who present for non-cardiac surgery should continue or discontinue these drugs preoperatively. Continuing the drugs entails the risk of perioperative refractory hypotension and/or angioneurotic oedema, while discontinuing the drugs entails the risk of rebound hypertension and myocardial ischaemia. The aim of this study is to evaluate the effect of continuation vs withholding of ACEIs/ARBs on mortality and other major outcomes in hypertensive patients undergoing elective non-cardiac surgery.

Methods

The continuing vs withholding of ACEIs/ARBs in patients undergoing non-cardiac surgery is a prospective, multi-centric, open-label randomised controlled trial. Two thousand one hundred hypertensive patients receiving ACEIs/ARBs and planned for elective non-cardiac surgery will be enrolled. They will be randomised to either continue the ACEIs/ARBs including on the day of surgery (group A) or to withhold it 24–36 h before surgery (group B). The primary endpoint will be the difference in the composite outcome of all-cause in-hospital/30-day mortality and major adverse cardiovascular and non-cardiovascular events. Secondary endpoints will be to evaluate the differences in perioperative hypotension, angioneurotic oedema, myocardial injury, ICU and hospital stay. The impact of the continuation vs withholding of the ACEIs/ARBs on the incidence of case cancellation will also be studied.

Discussion

The results of this trial should provide sufficient evidence on whether to continue or withhold ACEIs/ARBs before major non-cardiac surgery.

Trial registration

Clinical Trials Registry of India CTRI/2021/01/030199. Registered on 4 January 2021
Timing of transcranial direct current stimulation (tDCS) combined with speech and language therapy (SLT) for aphasia: study protocol for a randomized controlled trial
Authors: Ashaie Sameer A. , Engel Samantha , Cherney Leora R.
Published: August 2022

Background

Studies suggest that language recovery in aphasia may be improved by pairing speech-language therapy with transcranial direct current stimulation. However, results from many studies have been inconclusive regarding the impact transcranial direct current stimulation may have on language recovery in individuals with aphasia. An important factor that may impact the efficacy of transcranial direct current stimulation is its timing relative to speech-language therapy. Namely, online transcranial direct current stimulation (paired with speech-language therapy) and offline transcranial direct current stimulation (prior to or following speech-language therapy) may have differential effects on language recovery in post-stroke aphasia. Transcranial direct current stimulation provided immediately before speech-language therapy may prime the language system whereas stimulation provided immediately after speech-language therapy may aid in memory consolidation. The main aim of this study is to investigate the differential effects of offline and online transcranial direct stimulation on language recovery (i.e., conversation) in post-stroke aphasia.

Methods/design

The study is a randomized, parallel-assignment, double-blind treatment study. Participants will be randomized to one of four treatment conditions and will participate in 15 treatment sessions. All groups receive speech-language therapy in the form of computer-based script practice. Three groups will receive transcranial direct current stimulation: prior to speech-language therapy, concurrent with speech-language therapy, or following speech-language therapy. One group will receive sham stimulation (speech-language therapy only). We aim to include 12 participants per group (48 total). We will use fMRI-guided neuronavigation to determine placement of transcranial direct stimulation electrodes on participants’ left angular gyrus. Participants will be assessed blindly at baseline, immediately post-treatment, and at 4 weeks and 8 weeks following treatment. The primary outcome measure is change in the rate and accuracy of the trained conversation script from baseline to post-treatment.

Discussion

Results from this study will aid in determining the optimum timing to combine transcranial direct current stimulation with speech-language therapy to facilitate better language outcomes for individuals with aphasia. In addition, effect sizes derived from this study may also inform larger clinical trials investigating the impact of transcranial direct current stimulation on functional communication in individuals with aphasia.

Trial registration

ClinicalTrials.gov NCT03773406. December 12, 2018.
The CORE-KDT study: a mixed methods protocol to establish core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy
Authors: Carroll Jennifer H. , Cross J. Helen , Hickson Mary , Williams Emma , Aldridge Valerie , Collinson Avril
Published: August 2022

Background

A core outcome set defines the minimum outcomes that should be included in clinical trials, audit or practice. The aim being to increase the quality and relevance of research by ensuring consistency in the measurement and reporting of outcomes. Core outcome sets have been developed for a variety of disease states and treatments. However, there is no established set of core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy. This should be developed using a patient-centred approach to ensure the outcomes measured are relevant to patients and clinical practice.

Methods

This is a mixed methods study of four phases to develop a core outcome set for refractory childhood epilepsy treated with ketogenic diet therapy. In phase 1, a systematic scoping review of the literature will establish which outcomes are measured in trials of refractory epilepsy treated with ketogenic diet therapy. In phase 2, qualitative interviews with parents and carers will aim to identify the outcomes of importance to these stakeholders. Phase 3 will see a comprehensive list of outcomes collated from the first two phases, grouped into domains according to an outcome taxonomy. Phase 4 will invite parents, health care professionals and researchers to participate in a two-round Delphi study to rate the importance of the presented outcomes. Following which, the core outcome set will be ratified at a face to face consensus meeting.

Discussion

This study will guide outcome measurement in future studies of childhood epilepsy treated with ketogenic diet therapy and clinical practice through audit and service evaluation.
Efficacy and safety of Dengyinnaotong Capsule in patients with Cognitive impairment caused by cerebral Small Vessel Disease: study protocol of a multicenter, randomized, open-label, controlled trial (De-CSVD trial)
Authors: Li Yan-Xia , Li Jin-Cun , Tian Min , Zheng Mao-Yong , Zhang Li-Ping , Zhang Jin-Lu , Yu Feng , Li Yi-Zhao , Zhang Qing-Hua
Published: August 2022

Background

Cerebral small vessel disease (CSVD) is a common syndrome in the older population, with a prevalence ranging from 5% in subjects aged 50 years to almost 100% in those aged 90 years and older. It is regarded to be a major cause of vascular cognitive impairment. Existing prevention and treatment approaches have not yet shown ideal clinical outcomes. Dengyinnaotong Capsule has shown great potential for improving cognitive function. This trial (De-CSVD trial) is designed to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive function in patients with CSVD .

Methods

This multicenter, randomized, open-label, controlled trial is planned to recruit at least 270 patients with mild cognitive impairment related to CSVD in 25 centers in China. Recruitment started on 10 May 2021 and is foreseen to end on 31 December 2022. The final follow-up of participants will be completed by the end of March 2023. Participants will be randomized in a ratio of 1:1 to the experimental group (routine basic treatment plus Dengyinnaotong Capsule) or the control group (routine basic treatment). The primary outcome is the change in the Montreal Cognitive Assessment score from baseline to week 12. Secondary outcomes are changes in Shape Trail Test, Activities of Daily Living, Geriatric Depression Scale, and Dizziness Handicap Inventory score from baseline to week 12, new vascular events, and the changes in serum level of homocysteine, high-sensitivity C-reactive protein, and D-dimer from baseline to week 4 and 12, respectively. The exploratory outcome is the changes in the Tinetti performance-oriented mobility assessment score from baseline to week 12. Safety assessment is performed by monitoring vital signs, general biochemical examinations, 12-lead electrocardiogram examinations, and incidence of cardiovascular and cerebrovascular ischemia or bleeding events. Visits will be performed at week 0 (baseline, pre-randomization), week 4, and week 12 in the treatment period (post-randomization).

Discussion

This trial is the first to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive impairment in patients with CSVD. The findings of this study might provide convincing evidence regarding the efficacy of Dengyinnaotong Capsule in patients with mild cognitive impairment related to CSVD.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100045831. Registered on 25 April 2021.
Shoulder-specific rehabilitation combined with aerobic exercises versus solely shoulder-specific rehabilitation in patients with type 2 diabetes mellitus: study protocol for a randomized controlled superiority trial
Authors: Habechian Fernanda A. P. , Flores Quezada Mauricio E. , Cools Ann M. , Kjaer Birgitte Hougs , Cuevas Cid Rodrigo I. , Zanca Gisele G.
Published: August 2022

Background

Musculoskeletal disorders are very common in patients with diabetes mellitus (DM). The upper limb is one of the regions that is most frequently affected generally presenting limited joint mobility, pain, and a decreased muscle strength. Most clinical trials with a focus on shoulder musculoskeletal rehabilitation are carried out in patients who do not present DM. Thus, the purpose of the present study is to compare the effects of two distinct treatment protocols (conventional shoulder musculoskeletal rehabilitation combined with aerobic exercises versus solely conventional shoulder musculoskeletal rehabilitation) on shoulder pain, function, strength, kinematics, and supraspinatus tendon thickness in patients with type 2 DM after 12 weeks of intervention and a subsequent follow-up at week 20.

Methods

A randomized controlled superiority trial will be conducted. Participants with a clinical diagnosis of type 2 DM of both sexes, age between 40 and 70 years, presenting shoulder pain will be randomly assigned to one of the following groups: (1) conventional shoulder musculoskeletal rehabilitation combined with aerobic exercises; (2) solely conventional shoulder musculoskeletal rehabilitation. All individuals will be evaluated before starting the treatment protocol (baseline) and at the end of treatment (post 12 weeks) and as a follow-up at 20 weeks. The shoulder function assessed by the SPADI (Shoulder Pain and Disability Index) questionnaire will be considered as primary outcome; the secondary outcome will be shoulder pain, measured with NPRS scales. Other outcomes will include range of motion, measured using a digital inclinometer; isometric shoulder muscle strength, measured using a manual muscle dynamometer; shoulder kinematics, measured using three-dimensional inertial units measurement; supraspinatus tendon thickness, measured using an ultrasound; AGE accumulation, using a skin autofluorescence measurement; and HbA1c (hemoglobin a1c), fasting glucose and lipid profile measured by a simple blood test.

Discussion

DM is a highly prevalent disease and a public health problem worldwide, and the upper extremity musculoskeletal disorders in DM are barely recognized and largely underestimated. In this way, it would be interesting to analyze if the combination of aerobic exercises with conventional musculoskeletal rehabilitation protocols could generate better results in the functionality, pain, mobility and an improvement in the biochemical aspects related to the hyperglycemia of these patients compared to solely the conventional musculoskeletal rehabilitation.

Trial registration

ClinicalTrials.gov NCT04817514. Registered on March 26, 2021.
Post-operative rehabilitation using a digital healthcare system in patients who had undergone rotator cuff repair: protocol for a single-center randomized controlled trial
Authors: Chang Won Kee , Lee Jong In , Hwang Ji Hye , Lim Jae-Young
Published: August 2022

Background

Operative repair of a rotator cuff tear requires up to 12 weeks of post-operative (post-op) home-based rehabilitation. Maintaining patients’ compliance in the post-op rehabilitation program is a pivotal component for generating successful outcomes. By developing a post-op rehabilitation-oriented digital healthcare system and applying it in patients who had undergone rotator cuff repair, we aim to increase the efficacy of the rehabilitation program and raise patients’ compliance levels. Here, we present a protocol developed for comparing the efficacy of rehabilitation using a newly developed augmented reality (AR)-based digital healthcare system with that of conventional rehabilitation for post-op rehabilitation of rotator cuff repair.

Methods

This study will recruit a total of 115 patients who had undergone rotator cuff repair within 3 days after surgery. Patients will be randomly allocated to rehabilitation using an AR-based digital healthcare system (digital group) or conventional rehabilitation (conventional group). Patients in both groups will perform brochure-based exercises from the immediate post-op period to post-op 6 weeks. From post-op 6 weeks to 12 weeks, patients in the digital group will use the AR-based system for post-op exercises, whereas patients in the conventional group will continue brochure-based rehabilitation exercises. The primary outcome will be scores on the Simple Shoulder Test at post-op 12 weeks. Secondary outcomes include numeric rating scale scores for pain, measures of range of motion and muscle strength of the affected shoulder, grip strength of the affected arm, scores on the Disabilities of the Arm, Shoulder and Hand test, the Shoulder Pain and Disability Index, and the EuroQoL-5D-5L quality-of-life measure. Analyses will be conducted using an intention-to-treat approach.

Discussion

This study will examine the effectiveness of an AR-based digital healthcare system for post-op rehabilitation in the patients after rotator cuff repair. The study will add evidence for the application of digital healthcare systems in post-op rehabilitation.

Trial registration

ClinicalTrials.gov NCT04511377. Registered on 10 August 2020.
Varicella zoster-associated progressive lower cranial and upper cervical polyneuropathy: a case report
Authors: Jia Fangzhi , Ting Eugene R. , Ahn Joo Hyen , Duggins Andrew
Published: August 2022

Background

Multiple cranial neuropathies carry a wide range of differential diagnoses, and when combined with cerebrospinal fluid monocytosis they often suggest an infective etiology. Reactivation of varicella zoster virus has been associated with a wide range of neurological complications. Among the cranial nerves, the upper cranial nerves (trigeminal and facial nerves) are more commonly affected; there have been some reports of lower cranial polyneuropathies resulting from varicella zoster virus reactivation. However, polyneuropathy involving both the cranial and cervical nerves is rarely reported.

Case presentation

This report highlights the case of a 64-year-old Chinese man presenting with an acute, severe dysphagia and dysphonia secondary to herpes zoster-associated progressive polyneuropathy involving the lower cranial and upper cervical nerves, without any mucocutaneous manifestations.

Conclusions

To our knowledge, this is the first case of varicella zoster virus-associated cranial and cervical polyneuropathy in the literature. The report also highlights the poor sensitivity of varicella zoster virus DNA detection by polymerase chain reaction in the cerebrospinal fluid, and proposes that serology be routinely performed in such polymerase chain reaction-negative cases without a clear diagnosis.
Integrative analysis of plasma metabolomics and proteomics reveals the metabolic landscape of breast cancer
Authors: An Rui , Yu Haitao , Wang Yanzhong , Lu Jie , Gao Yuzhen , Xie Xinyou , Zhang Jun
Published: August 2022

Background

Breast cancer (BC) is the most commonly diagnosed cancer. Currently, mammography and breast ultrasonography are the main clinical screening methods for BC. Our study aimed to reveal the specific metabolic profiles of BC patients and explore the specific metabolic signatures in human plasma for BC diagnosis.

Methods

This study enrolled 216 participants, including BC patients, benign patients, and healthy controls (HC) and formed two cohorts, one training cohort and one testing cohort. Plasma samples were collected from each participant and subjected to perform nontargeted metabolomics and proteomics. The metabolic signatures for BC diagnosis were identified through machine learning.

Results

Metabolomics analysis revealed that BC patients showed a significant change of metabolic profiles compared to HC individuals. The alanine, aspartate and glutamate pathways, glutamine and glutamate metabolic pathways, and arginine biosynthesis pathways were the critical biological metabolic pathways in BC. Proteomics identified 29 upregulated and 2 downregulated proteins in BC. Our integrative analysis found that aspartate aminotransferase (GOT1), l-lactate dehydrogenase B chain (LDHB), glutathione synthetase (GSS), and glutathione peroxidase 3 (GPX3) were closely involved in these metabolic pathways. Support vector machine (SVM) demonstrated a predictive model with 47 metabolites, and this model achieved a high accuracy in BC prediction (AUC = 1). Besides, this panel of metabolites also showed a fairly high predictive power in the testing cohort between BC vs HC (AUC = 0.794), and benign vs HC (AUC = 0.879).

Conclusions

This study uncovered specific changes in the metabolic and proteomic profiling of breast cancer patients and identified a panel of 47 plasma metabolites, including sphingomyelins, glutamate, and cysteine could be potential diagnostic biomarkers for breast cancer.
Chromosomal instability in adult-type diffuse gliomas
Authors: Richardson Timothy E. , Walker Jamie M. , Abdullah Kalil G. , McBrayer Samuel K. , Viapiano Mariano S. , Mussa Zarmeen M. , Tsankova Nadejda M. , Snuderl Matija , Hatanpaa Kimmo J.
Published: August 2022

Chromosomal instability (CIN) is a fundamental property of cancer and a key underlying mechanism of tumorigenesis and malignant progression, and has been documented in a wide variety of cancers, including colorectal carcinoma with mutations in genes such as APC. Recent reports have demonstrated that CIN, driven in part by mutations in genes maintaining overall genomic stability, is found in subsets of adult-type diffusely infiltrating gliomas of all histologic and molecular grades, with resulting elevated overall copy number burden, chromothripsis, and poor clinical outcome. Still, relatively few studies have examined the effect of this process, due in part to the difficulty of routinely measuring CIN clinically. Herein, we review the underlying mechanisms of CIN, the relationship between chromosomal instability and malignancy, the prognostic significance and treatment potential in various cancers, systemic disease, and more specifically, in diffusely infiltrating glioma subtypes. While still in the early stages of discovery compared to other solid tumor types in which CIN is a known driver of malignancy, the presence of CIN as an early factor in gliomas may in part explain the ability of these tumors to develop resistance to standard therapy, while also providing a potential molecular target for future therapies.
Effects of Lactiplantibacillus plantarum inoculation on the quality and bacterial community of whole-crop corn silage at different harvest stages
Authors: Dong Jianan , Li Songze , Chen Xue , Sun Zhe , Sun Yue , Zhen Yuguo , Qin Guixin , Wang Tao , Demelash Natnael , Zhang Xuefeng
Published: August 2022

Background

Silage is achieved by anaerobic fermentation of lactic acid bacteria. However, harvest stage andLactiplantibacillus plantarum(L. plantarum) content affect the changes of microbial community in silage, which play an important role in silage quality and mycotoxin levels. The current study evaluated the effects exerted by the application ofL. plantarumon fermentation, mycotoxins and bacterial community of whole-crop corn silage at different harvest stages. The fresh whole plant corn from the same area was harvested during the milk stage and the dough stage, following which from each harvest stage was subjected to fourL. plantarumtreatments: 0 cfu/g; 1 × 106 cfu/g; 1 × 107 cfu/g; and 1 × 108 cfu/g in a 2 × 4 factorial experimental design. Samples were collected on days 0, 3, 7, 21 and 42. Subsequently, nutrition parameters, fermentation parameters, mycotoxin levels and bacterial community were determined.

Results

Prolonging the harvest stage resulted in an increase in the levels of starch and dry matter as well as deoxynivalenol in corn silage. Addition of 1 × 107 cfu/g and 1 × 108 cfu/g ofL. plantarumapplied after 42 d of ensilage reduced dry matter loss, which significantly lowered deoxynivalenol concentration in corn silage at the dough stage (P < 0.01). The pH of corn silage decreased, whereas the lactic acid concentration increased after ensiling. The effects exerted by the interaction (harvest stage × dose ofL. plantarum) on pH on day 21 as well as on fermentation and lactic acid on days 21 and 42 were significant (P < 0.05). Addition of 1 × 107 cfu/g ofL. plantarumat the dough stage significantly increased the relative abundance of Firmicutes while decreasing that of Bacteroidetes, compared to whenL. plantarumwas not added (P < 0.05).

Conclusions

AddingL. plantarumimproved the fermentation quality and bacterial community of silage, which reduced part of mycotoxin content and relative abundance of harmful bacteria. In addition, addingL. plantarumin dough stage resulted in greater improvements to mycotoxin content and bacterial community.