bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Account of the Perceptions and Market Determinants of Indigenous Cow Milk Sector in India
Authors: Iyengar Vijayalakshmi
Published: January 2024

The conventional milk market in India has evolved in India over the last five decades post the ‘Operations Flood Milk Revolution’. During the 1950s and 60s indigenous cows were cross-pollinated with foreign breeds to fulfil the shortfall in the local demand for milk. The cross-pollination of exotic with Indian breeds contaminated the purity of the lineage of Indian cow breeds which had a rich nutritive pedigree. Over the last six years, there has been a fresh stream of indigenous milk market that is slowly emerging alongside the conventional market (cross-breed milk) under the name of ‘Desi Cow Milk’. This milk is marketed as an extract of pure Indian indigenous cows like Gir, Sahiwal, Tharparker, Khilar etc. The market is niche; but is available at varying price points from 90 I. a litre to 240 I. a litre. Consumers have mixed opinions about this market while others know little of this market. Ayurvedic doctors are prescribing this desi milk as a cure for several chronic diseases like diabetes, cancer, skin allergies, autism etc. Word-of-mouth publicity is a strong promotion channel and business is governed more by trust. This paper is an attempt to demystify the perceptions about the Desi cow milk market and identifies the determinants that govern its growth if it were to become a full-fledged market in future. The paper is qualitative and explores a sample size of 30 using an open-ended questionnaire.
The base metal sulfide and Ni–Co arsenide-bearing veins of Valsassina, Lombardy, Italy: a preliminary study
Authors: Vergani Fabrizio , Moroni Marilena , Gentile Paolo , Gatta G. Diego
Published: January 2024

Valsassina (Lombardy, Northern Italy) is located in the Lombard Southern Alps and is characterised by the presence of a metamorphic basement, by a major late Variscan intrusive complex and by Carboniferous–Permian volcano-sedimentary cover units. These rocks host a pervasive system of inadequately studied mineralised veins. These veins are characterised by base metal (Pb, Zn, Cu and Fe) and complex polymetallic assemblages.

In this study, we have investigated the ore textures, mineral compositions of sulfides and sulfosalts (by EMPA–WDS and LA–ICP–MS analyses), and stable isotopes (C and O) in carbonate gangue minerals of various mineralised veins to determine the conditions of deposition of these ore deposits. Two different vein families can be recognised in Valsassina: NNW–SSE veins characterised by a complex polymetallic sulfide–sulfosalt assemblage, also with Ni–Co–Fe arsenides and other Ag–Bi-bearing minerals; and NE–SW veins with a simpler, base metal sulfide assemblage. The Ni–Co-bearing NNW–SSE veins have some distinctive features of the ‘five-element vein’ type deposits, with the Ni–Co–Fe arsenide ore stage pre-dating a sulfide-tetrahedrite-dominated ore stage. LA–ICP–MS data for pyrite and sphalerite, and stable isotopic compositions (C and O) of the carbonate gangue minerals, show no clear differences between the two families of veins, which are probably linked genetically. The isotopic compositions of the Valsassina vein carbonates are closely comparable with the signature of several major five-element ore districts. Preliminary temperature estimates for the Valsassina vein systems were based on the sphalerite composition, applying the GGIMFis geothermometer. The estimated temperatures for the sulfide-dominated ore stage post-dating the Ni–Co minerals precipitation range between 100 and 250°C. The crosscutting relationships, observed for all the veins with the host rocks, suggest a possible late to post Variscan (late Permian) age, making these vein systems comparable with other late–post Variscan polyphase hydrothermal events affecting large sectors of the Southern Alpine domain.
Possible melatonin-induced salt stress tolerance pathway in Phaseolus vulgaris L. using transcriptomic and metabolomic analyses
Authors: Yang Xiaoxu , Liu Dajun , Liu Chang , Li Mengdi , Yan Zhishan , Zhang Yu , Feng Guojun
Published: January 2024

Melatonin plays important roles in multiple stress responses; however, the downstream signaling pathway and molecular mechanism remain unclear. This study aimed to elucidate the transcriptional regulation of melatonin-induced salt stress tolerance in Phaseolus vulgaris L. and identify the key downstream transcription factors of melatonin through transcriptomic and metabolomic analyses. The melatonin-induced transcriptional network of hormones, transcription factors, and functional genes was established under both control and stress conditions. Among these, eight candidate transcription factors were identified via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, one gene related to transmembrane transport of salts (Phvul.004G177300). These genes may play a role in maintaining the cell structure and excreting sodium ions outside the cell or transporting them to the vacuoles for storage. Melatonin regulates the Phvul.009G210332 gene and metabolites C05642 (N-acetyl-N-2-formyl-5-methoxycanurine), C05643 (6-hydroxymelatonin), C05660 (5-methoxyindoleacetic acid) involved in tryptophan metabolism. The metabolites C05642 and C05643 were identified as decomposition products of tryptophan, indicating that exogenous melatonin entered the P. vulgaris tissue and was metabolized. Melatonin promotes the synthesis and metabolism of tryptophan, which is crucial to plant metabolism, growth, maintenance, and repair.
Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong
Authors: Chow Victor Yung Sin , Cheung Wing I
Published: January 2024

Background & aim

To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality.

Methods

Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development.

Results

During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3–8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy.

Conclusions

The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.
A case of Wilson’s disease combined with intracranial lipoma and dysplasia of the corpus callosum with review of the literature
Authors: Zhang Liangjie , Zhu Ling , Ci Chunling , Ai Wenlong , Wang Yu , Wang Xun
Published: January 2024

Background

Wilson’s disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence.

Case presentation

The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson’s disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson’s disease combined with intracranial lipoma and corpus callosum dysplasia. The patient’s WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient’s abnormal copper metabolism may promote the growth of intracranial lipoma.

Conclusion

The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases’ more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.
Clinical activity and safety of sintilimab, bevacizumab, and TMZ in patients with recurrent glioblastoma
Authors: Lu Yinghao , Liao Limin , Du Kunpeng , Mo Jianhua , Zou Xia , Liang Junxian , Chen Jiahui , Tang Wenwen , Su Liwei , Wu Jieping , Zhang Junde , Tan Yujing
Published: January 2024

Purpose

There are limited and no standard therapies for recurrent glioblastoma. We herein report the antitumour activity and safety of sintilimab, bevacizumab and temozolomide (TMZ) in recurrent glioblastoma.

Methods

We retrospectively analysed eight patients with recurrent glioblastoma treated with sintilimab (200 mg) every three weeks + bevacizumab (10 mg/kg) every three weeks + TMZ (200 mg/m²orally) (5 days orally every 28 days for a total of four weeks). The primary objective was investigator-assessed median progression-free survival(mPFS). Secondary objectives were to assess the 6-month PFS, objective response rate (ORR) and duration of response (DOR) accroding to RANO criteria.

Results

The mPFS time for 8 patients was 3.340 months (95% CI: 2.217–4.463), The longest PFS was close to 9 months. Five patients were assessed to have achieved partial response (PR), with an overall remission rate of 62.5%, Four patients experienced a change in tumour volume at the best response time of greater than 60% shrinkage from baseline, and one patient remained progression free upon review, with a DOR of more than 6.57 months. The 6-month PFS was 25% (95% CI: 5.0–55.0%). Three patients had a treatment-related adverse events, though no grade 4 or 5 adverse events occurred.

Conclusion

In this small retrospective study, the combination regimen of sintilimab, bevacizumab and TMZ showed promising antitumour activity in treatment of recurrent glioblastoma, with a good objective remission rate.
Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer
Authors: Yang Zheng-Jun , Xin Fei , Chen Zu-Jin , Yu Yue , Wang Xin , Cao Xu-Chen
Published: January 2024

Background

Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.

Methods

This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.

Results

The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68–0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index < 30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.

Conclusions

Patients with ER-negative, PR-negative, HER2 3 + and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.
Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma
Authors: Tian He , Wei Ran , Xiao Chu , Fan Tao , Che Yun , Liu Tiejun , Zheng Bo , Li Chunxiang , He Jie
Published: January 2024

Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients’ poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.
Effect of neuromuscular electrical stimulation in critically ill adults with mechanical ventilation: a systematic review and network meta-analysis
Authors: Xu Cuiping , Yang Feng , Wang Qimin , Gao Wei
Published: January 2024

Background

Neuromuscular electrical stimulation (NMES) is widely used as a rehabilitation methods to restore muscle mass and function in prolonged immobilization individuals. However, its effect in mechanically ventilated patients to improve clinical outcomes remains unclear.

Methods

A comprehensive search was conducted using PubMed, Embase, Web of Science, PEDro, and the Cochrane Library from their inception until December 24th, 2023. The search targeted randomized controlled trials (RCTs) comparing NMES with physical therapy (PT) or usual ICU care (CG), for improving clinical outcomes in mechanically ventilated patients. We performed a network meta-analysis utilizing Stata version 14.0 and R 4.3.1.

Results

We included 23 RCTs comprising 1312 mechanically ventilated adults. The treatments analyzed were NMES, PT, NMES combined with PT (NMES+PT), and CG. Network meta-analyses revealed that NMES or NMES+PT significantly improved extubation success rate compared to CG, with ORs of 1.85 (95% CI: 1.11, 3.08) and 5.89 (95% CI: 1.77, 19.65), respectively. Additionally, NMES exhibited a slight decrease in extubation success rate compared with NMES+PT, with OR of 0.31 (95% CI: 0.11, 0.93). Nevertheless, neither NMES nor NMES+PT showed any significant improvement in ICU length of stay (LOS), ventilation duration, or mortality when compared with PT or CG. NMES+PT emerged as the most effective strategy for all considered clinical outcomes according to the ranking probabilities. The evidence quality ranged from “low” to “very low” in this network meta-analysis.

Conclusions

NMES appears to be a straightforward and safe modality for critically ill, mechanically ventilated patients. When combined with PT, it significantly improved the extubation success rate against standard ICU care and NMES alone, and showed a better ranking over PT or NMES alone for clinical outcomes. Therefore, NMES combined with PT may be a superior rehabilitation strategy for this patient group.
Bereaved parents’ perceptions of memory making: a qualitative meta-synthesis
Authors: Xu Dan-dan , Zhang Guang-xiong , Ding Xin-bo , Ma Jing , Suo Ya-xi , Peng Yang-yao , Zeng Ji-li , Liu Miao , Hou Rui-tong , Li Jin , Hu Fen
Published: January 2024

Objective

This study aims to investigate the experiences of parents who have experienced bereavement in their efforts to preserve memories of their deceased child.

Methods

Employing a qualitative meta-synthesis approach, this study systematically sought relevant qualitative literature by conducting searches across various electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Wiley, up until July 2023.

Results

Nine studies are eligible for inclusion and included in the meta-synthesis. Three overarching categories are identified: (1) Affirming the Significance of Memory Making. (2) Best Practices in Memory Making. (3) Barriers to Effective Memory Making.

Conclusion

Bereaved parents highly value the act of creating lasting memories, emphasizing its profound significance. While forming these memories, it is imperative to offer family-centered care and honor diverse preferences and needs. It is essential to offer effective support to parents, offering them a range of choices. Furthermore, a more comprehensive examination of memory-making practices is required to better understand their influence on parents’ recollections of their deceased child.
A high-performance computational workflow to accelerate GATK SNP detection across a 25-genome dataset
Authors: Zhou Yong , Kathiresan Nagarajan , Yu Zhichao , Rivera Luis F. , Yang Yujian , Thimma Manjula , Manickam Keerthana , Chebotarov Dmytro , Mauleon Ramil , Chougule Kapeel , Wei Sharon , Gao Tingting , Green Carl D. , Zuccolo Andrea , Xie Weibo , Ware Doreen , Zhang Jianwei , McNally Kenneth L. , Wing Rod A.
Published: January 2024

Background

Single-nucleotide polymorphisms (SNPs) are the most widely used form of molecular genetic variation studies. As reference genomes and resequencing data sets expand exponentially, tools must be in place to call SNPs at a similar pace. The genome analysis toolkit (GATK) is one of the most widely used SNP calling software tools publicly available, but unfortunately, high-performance computing versions of this tool have yet to become widely available and affordable.

Results

Here we report an open-source high-performance computing genome variant calling workflow (HPC-GVCW) for GATK that can run on multiple computing platforms from supercomputers to desktop machines. We benchmarked HPC-GVCW on multiple crop species for performance and accuracy with comparable results with previously published reports (using GATK alone). Finally, we used HPC-GVCW in production mode to call SNPs on a “subpopulation aware” 16-genome rice reference panel with ~ 3000 resequenced rice accessions. The entire process took ~ 16 weeks and resulted in the identification of an average of 27.3 M SNPs/genome and the discovery of ~ 2.3 million novel SNPs that were not present in the flagship reference genome for rice (i.e., IRGSP RefSeq).

Conclusions

This study developed an open-source pipeline (HPC-GVCW) to run GATK on HPC platforms, which significantly improved the speed at which SNPs can be called. The workflow is widely applicable as demonstrated successfully for four major crop species with genomes ranging in size from 400 Mb to 2.4 Gb. Using HPC-GVCW in production mode to call SNPs on a 25 multi-crop-reference genome data set produced over 1.1 billion SNPs that were publicly released for functional and breeding studies. For rice, many novel SNPs were identified and were found to reside within genes and open chromatin regions that are predicted to have functional consequences. Combined, our results demonstrate the usefulness of combining a high-performance SNP calling architecture solution with a subpopulation-aware reference genome panel for rapid SNP discovery and public deployment.
Interpretable artificial intelligence-based app assists inexperienced radiologists in diagnosing biliary atresia from sonographic gallbladder images
Authors: Zhou Wenying , Ye Zejun , Huang Guangliang , Zhang Xiaoer , Xu Ming , Liu Baoxian , Zhuang Bowen , Tang Zijian , Wang Shan , Chen Dan , Pan Yunxiang , Xie Xiaoyan , Wang Ruixuan , Zhou Luyao
Published: January 2024

Background

A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model’s performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings.

Methods

A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC).

Results

The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists.

Conclusions

The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.
Dysfunction in endocannabinoids, palmitoylethanolamide, and degradation of tryptophan into kynurenine in individuals with depressive symptoms
Authors: Comai Stefano , Nunez Nicolas , Atkin Tobias , Ghabrash Maykel F. , Zakarian Rita , Fielding Allan , Saint-Laurent Marie , Low Nancy , Sauber Garrett , Ragazzi Eugenio , Hillard Cecilia J. , Gobbi Gabriella
Published: January 2024

Background

The endocannabinoid (eCB) system and the serotonin (5-HT) are both implicated in the severity of the depression. 5-HT is synthesized from the amino acid tryptophan (Trp), which is also a precursor for kynurenine (Kyn) whose production is increased at the expense of 5-HT in depressed patients. No clinical studies have investigated the crosstalk between the eCB system and the Trp/5-HT/Kyn pathways. Here, we hypothesized that the eCB system is associated with an enhanced Kyn production in relation to the severity of depressive symptoms.

Methods

Eighty-two subjects (51 patients with a diagnosis of depressive disorder (DSM-5) and 31 healthy volunteers), were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Scale, and Global Clinical Impression. Serum concentrations of eCBs (N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG)); structurally related fatty acyl compounds 2-oleoylglycerol (2-OG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA); Trp, Kyn, Kyn/Trp ratio (an index of Trp degradation into Kyn) and 5-HT were also determined.

Results

Following a principal component analysis including the severity of depression, Kyn and the Kyn/Trp ratio appear to be directly associated with 2-AG, AEA, and PEA. Interestingly, these biomarkers also permitted to distinguish the population into two main clusters: one of individuals having mild/severe depressive symptoms and the other with an absence of depressive symptoms. Using parametric analysis, higher serum levels of 2-AG, Kyn, and the ratio Kyn/Trp and lower levels of Trp and 5-HT were found in individuals with mild/severe depressive symptoms than in those without depressive symptoms. While in asymptomatic people, PEA was directly associated to Trp, and OEA indirectly linked to 5-HT, in individuals with depressive symptoms, these correlations were lost, and instead, positive correlations between AEA and 2-AG, PEA and AEA, and PEA vs 2-AG and OEA concentrations were found.

Conclusions

Parametric and non-parametric analyses suggest a possible association between eCBs, tryptophan/kynurenine biomarkers, and severity of depression, confirming a likely interplay among inflammation, stress, and depression. The enhanced relationships among the biomarkers of the 2-AG and AEA pathways and related lipids seen in individuals with depressive symptoms, but not in asymptomatics, suggest an altered metabolism of the eCB system in depression.
Predicting cognitive scores from wearable-based digital physiological features using machine learning: data from a clinical trial in mild cognitive impairment
Authors: Rykov Yuri G. , Patterson Michael D. , Gangwar Bikram A. , Jabar Syaheed B. , Leonardo Jacklyn , Ng Kok Pin , Kandiah Nagaendran
Published: January 2024

Background

Continuous assessment and remote monitoring of cognitive function in individuals with mild cognitive impairment (MCI) enables tracking therapeutic effects and modifying treatment to achieve better clinical outcomes. While standardized neuropsychological tests are inconvenient for this purpose, wearable sensor technology collecting physiological and behavioral data looks promising to provide proxy measures of cognitive function. The objective of this study was to evaluate the predictive ability of digital physiological features, based on sensor data from wrist-worn wearables, in determining neuropsychological test scores in individuals with MCI.

Methods

We used the dataset collected from a 10-week single-arm clinical trial in older adults (50–70 years old) diagnosed with amnestic MCI (N = 30) who received a digitally delivered multidomain therapeutic intervention. Cognitive performance was assessed before and after the intervention using the Neuropsychological Test Battery (NTB) from which composite scores were calculated (executive function, processing speed, immediate memory, delayed memory and global cognition). The Empatica E4, a wrist-wearable medical-grade device, was used to collect physiological data including blood volume pulse, electrodermal activity, and skin temperature. We processed sensors’ data and extracted a range of physiological features. We used interpolated NTB scores for 10-day intervals to test predictability of scores over short periods and to leverage the maximum of wearable data available. In addition, we used individually centered data which represents deviations from personal baselines. Supervised machine learning was used to train models predicting NTB scores from digital physiological features and demographics. Performance was evaluated using “leave-one-subject-out” and “leave-one-interval-out” cross-validation.

Results

The final sample included 96 aggregated data intervals from 17 individuals. In total, 106 digital physiological features were extracted. We found that physiological features, especially measures of heart rate variability, correlated most strongly to the executive function compared to other cognitive composites. The model predicted the actual executive function scores with correlation r = 0.69 and intra-individual changes in executive function scores with r = 0.61.

Conclusions

Our findings demonstrated that wearable-based physiological measures, primarily HRV, have potential to be used for the continuous assessments of cognitive function in individuals with MCI.
Prognostic significance and survival benefits of postoperative adjuvant chemotherapy in patients with stage IA lung adenocarcinoma with non-predominant micropapillary components
Authors: Li Rongyang , Qiu Jianhao , Li Zhenyi , Li Haiming , Tang Zhanpeng , Yu Wenhao , Tian Hui , Sun Zhenguo
Published: January 2024

Background

The prognostic significance of adjuvant chemotherapy (ACT) for patients with stage IA micropapillary non-predominant (MPNP) lung adenocarcinoma (LUAD) remains unknown. This study aimed to investigate the effects of postoperative ACT in patients with stage IA MPNP-LUAD.

Methods

A total of 149 patients with pathological stage IA MPNP-LUAD who underwent surgery at our center were retrospectively analyzed. Propensity score matching (PSM) analysis was conducted to reduce potential selection bias. Kaplan–Meier analyses were used to assess the impact of ACT on recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Subgroup analyses were performed for the survival outcomes based on the percentage of micropapillary components. Cox proportional hazards regression analyses were applied to identify risk factors associated with survival.

Results

The receipt or non-receipt of postoperative ACT had no significant effect on RFS, OS, and DSS among all enrolled patients with stage IA MPNP-LUAD (P > 0.05). For patients with a micropapillary component > 5%, the 5-year rates of RFS, OS, and DSS were significantly higher in the ACT group compared to the observation group, both before and after PSM (P < 0.05). However, the differences between the two groups were not significant for patients with a micropapillary component ≤ 5% (P > 0.05). The resection range (HR = 0.071; 95% CI: 0.020–0.251; P < 0.001), tumor size (HR = 2.929; 95% CI: 1.171–7.330; P = 0.022), and ACT (HR = 0.122; 95% CI: 0.037–0.403; P = 0.001) were identified as independent prognostic factors for RFS through Cox regression analysis.

Conclusion

Patients with stage IA MPNP-LUAD who have a micropapillary component greater than 5% might benefit from postoperative ACT, while those with a micropapillary component ≤ 5% did not appear to derive the same benefit from postoperative ACT.
Intratumoral microorganisms in tumors of the digestive system
Authors: Xuan Mengjuan , Gu Xinyu , Liu Yingru , Yang Li , Li Yi , Huang Di , Li Juan , Xue Chen
Published: January 2024

Tumors of the digestive system pose a significant threat to human health and longevity. These tumors are associated with high morbidity and mortality rates, leading to a heavy economic burden on healthcare systems. Several intratumoral microorganisms are present in digestive system tumors, and their sources and abundance display significant heterogeneity depending on the specific tumor subtype. These microbes have a complex and precise function in the neoplasm. They can facilitate tumor growth through various mechanisms, such as inducing DNA damage, influencing the antitumor immune response, and promoting the degradation of chemotherapy drugs. Therefore, these microorganisms can be targeted to inhibit tumor progression for improving overall patient prognosis. This review focuses on the current research progress on microorganisms present in the digestive system tumors and how they influence the initiation, progression, and prognosis of tumors. Furthermore, the primary sources and constituents of tumor microbiome are delineated. Finally, we summarize the application potential of intratumoral microbes in the diagnosis, treatment, and prognosis prediction of digestive system tumors.
Effects of remote coaching following supervised exercise oncology rehabilitation on physical activity levels, physical fitness, and patient-reported outcomes: a randomised controlled trial
Authors: Weemaes Anouk T.R. , Beelen Milou , Weijenberg Matty P. , van Kuijk Sander M. J. , Lenssen Antoine F.
Published: January 2024

Background

Studies have shown that cancer survivors experience difficulties maintaining physical activity levels after participation in a supervised exercise rehabilitation program. This study aimed to assess the effectiveness of a six-month remote coaching intervention, following a supervised exercise oncology rehabilitation program on maintenance of PA levels; and improvement of aerobic capacity, muscle strength and patient-reported outcomes in cancer survivors.

Methods

Ninety-seven participants from a Dutch University Hospital’s exercise rehabilitation program were randomised to the COACH group (n = 46), receiving 6 months of remote coaching after completing the exercise program, or the CONTROL group (n = 50), receiving no additional intervention. Assessment of PA levels; sedentary time; aerobic capacity; muscle strength; fatigue; health-related quality of life (HRQoL); level of anxiety and depression; and return to work (RTW) rates were conducted at baseline (T0) and six months later (T1). Multiple linear regression was used for between-group statistical comparisons of all outcomes measures. Mean differences at T1 were estimated with corresponding 95% confidence intervals (95%CI).

Results

No significant between-group differences were observed for all outcomes at T1. An adjusted mean difference in weekly PA of 45 min (95%CI -50;140) was observed between the COACH group and the CONTROL group, favouring the COACH group, yet lacking statistical or clinical significance.

Conclusions

Our six-month remote coaching intervention did not notably improve PA levels; sedentary time; aerobic capacity; muscle strength; HRQoL; fatigue; anxiety and depression symptoms and RTW rates after participation in a supervised exercise oncology program. Although the participants who received coaching showed slightly higher levels of PA, these differences were not significant. More research is needed to identify patients in need for follow-up interventions following supervised exercise program and to investigate the effectiveness of remote coaching interventions in these patients.

Trial registration

Dutch Trial Register NL7729, registered 13 may 2019, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7729.
The glucocorticoid receptor as a master regulator of the Müller cell response to diabetic conditions in mice
Authors: Pfaller Anna M. , Kaplan Lew , Carido Madalena , Grassmann Felix , Díaz-Lezama Nundehui , Ghaseminejad Farhad , Wunderlich Kirsten A. , Glänzer Sarah , Bludau Oliver , Pannicke Thomas , Weber Bernhard H. F. , Koch Susanne F. , Bonev Boyan , Hauck Stefanie M. , Grosche Antje
Published: January 2024

Diabetic retinopathy (DR) is considered a primarily microvascular complication of diabetes. Müller glia cells are at the centre of the retinal neurovascular unit and play a critical role in DR. We therefore investigated Müller cell-specific signalling pathways that are altered in DR to identify novel targets for gene therapy. Using a multi-omics approach on purified Müller cells from diabetic db/db mice, we found the mRNA and protein expression of the glucocorticoid receptor (GR) to be significantly decreased, while its target gene cluster was down-regulated. Further, oPOSSUM TF analysis and ATAC- sequencing identified the GR as a master regulator of Müller cell response to diabetic conditions. Cortisol not only increased GR phosphorylation. It also induced changes in the expression of known GR target genes in retinal explants. Finally, retinal functionality was improved by AAV-mediated overexpression of GR in Müller cells. Our study demonstrates an important role of the glial GR in DR and implies that therapeutic approaches targeting this signalling pathway should be aimed at increasing GR expression rather than the addition of more ligand.

Graphical Abstract
Exosome-mediated regulation of inflammatory pathway during respiratory viral disease
Authors: Gheitasi Hamidreza , Sabbaghian Mohammad , Shekarchi Ali Akbar , Mirmazhary Amir Ali , Poortahmasebi Vahdat
Published: January 2024

Viruses have developed many mechanisms by which they can stimulate or inhibit inflammation and cause various diseases, including viral respiratory diseases that kill many people every year. One of the mechanisms that viruses use to induce or inhibit inflammation is exosomes. Exosomes are small membrane nanovesicles (30–150 nm) released from cells that contain proteins, DNA, and coding and non-coding RNA species. They are a group of extracellular vesicles that cells can take up to produce and mediate communication. Intercellular effect exosomes can deliver a broad confine of biological molecules, containing nucleic acids, proteins, and lipids, to the target cell, where they can convey therapeutic or pathogenic consequences through the modulation of inflammation and immune processes. Recent research has shown that exosomes can deliver entire virus genomes or virions to distant target cells, then the delivered viruses can escape the immune system and infect cells. Adenoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial viruses, picornaviruses, coronaviruses, and rhinoviruses are mostly related to respiratory diseases. In this article, we will first discuss the current knowledge of exosomes. We will learn about the relationship between exosomes and viral infections, and We mention the inflammations caused by viruses in the airways, the role of exosomes in them, and finally, we examine the relationship between the viruses as mentioned earlier, and the regulation of inflammatory pathways that play a role in causing the disease.
Tailored implementation of national recommendations on fall prevention among older adults in municipalities in Norway (FALLPREVENT trial): a study protocol for a cluster-randomised trial
Authors: Bjerk Maria , Flottorp Signe A. , Pripp Are Hugo , Øien Henning , Hansen Tonya Moen , Foy Robbie , Close Jacqueline , Linnerud Siv , Brovold Therese , Solli Rune , Olsen Nina Rydland , Skelton Dawn A. , Rydwik Elisabeth , Helbostad Jorunn L. , Idland Gro , Kvæl Linda , Vieira Edgar , Taraldsen Kristin
Published: January 2024

Background

Despite substantial research evidence indicating the effectiveness of a range of interventions to prevent falls, uptake into routine clinical practice has been limited by several implementation challenges. The complexity of fall prevention in municipality health care underlines the importance of flexible implementation strategies tailored both to general determinants of fall prevention and to local contexts. This cluster-randomised trial (RCT) investigates the effectiveness of a tailored intervention to implement national recommendations on fall prevention among older home-dwelling adults compared to usual practice on adherence to the recommendations in health professionals.

Methods

Twenty-five municipalities from four regions in Norway will be randomised to intervention or control arms. Each municipality cluster will recruit up to 30 health professionals to participate in the study as responders. The tailored implementation intervention comprises four components: (1) identifying local structures for implementation, (2) establishing a resource team from different professions and levels, (3) promoting knowledge on implementation and fall prevention and (4) supporting the implementation process. Each of these components includes several implementation activities. The Consolidated Framework for Implementation Research (CFIR) will be used to categorise determinants of the implementation process and the Expert Recommendations for Implementing Change (ERIC) will guide the matching of barriers to implementation strategies. The primary outcome measure for the study will be health professionals’ adherence to the national recommendations on fall prevention measured by a questionnaire. Secondary outcomes include injurious falls, the feasibility of the intervention, the experiences of the implementation process and intervention costs. Measurements will be carried out at baseline in August 2023, post-intervention in May 2024 and at a follow-up in November 2024.

Discussion

This study will provide evidence on the effectiveness, intervention costs and underlying processes of change of tailored implementation of evidence-based fall prevention recommendations.

Trial registration

The trial is registered in the Open Science Registry: https://doi.org/10.17605/OSF.IO/JQ9T5. Registered: March 03, 2023.
Monte Carlo simulation of the Varian TrueBeam flattened-filtered beams using a surrogate geometry in PRIMO
Authors: Rodriguez Miguel , Sempau Josep , Brualla Lorenzo
Published: January 2024

Background

Monte Carlo simulation of radiation transport for medical linear accelerators (linacs) requires accurate knowledge of the geometrical description of the linac head. Since the geometry of Varian TrueBeam machines has not been disclosed, the manufacturer distributes phase-space files of the linac patient-independent part to allow researchers to compute absorbed dose distributions using the Monte Carlo method. This approach limits the possibility of achieving an arbitrarily small statistical uncertainty. This work investigates the use of the geometry of the Varian Clinac 2100, which is included in the Monte Carlo system PRIMO, as a surrogate.

Methods

Energy, radial and angular distributions extracted from the TrueBeam phase space files published by the manufacturer and from phase spaces tallied with PRIMO for the Clinac 2100 were compared for the 6, 8, 10 and 15 MV flattened-filtered beams. Dose distributions in water computed for the two sets of PSFs were compared with the Varian Representative Beam Data (RBD) for square fields with sides ranging from 3 to 30 cm. Output factors were calculated for square fields with sides ranging from 2 to 40 cm.

Results

Excellent agreement with the RBD was obtained for the simulations that employed the phase spaces distributed by Varian as well as for those that used the surrogate geometry, reaching in both cases Gamma ($$2\%$$

2
%

, 2 mm) pass rates larger than $$99\%$$

99
%

, except for the 15 MV surrogate. This result supports previous investigations that suggest a change in the material composition of the TrueBeam 15 MV flattening filter. In order to get the said agreement, PRIMO simulations were run using enlarged transport parameters to compensate the discrepancies between the actual and surrogate geometries.

Conclusions

This work sustains the claim that the simulation of the 6, 8 and 10 MV flattening-filtered beams of the TrueBeam linac can be performed using the Clinac 2100 model of PRIMO without significant loss of accuracy.
Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study
Authors: Zhao Longmei , Zhou Shasha , Wang SiWei , Wu Rui , Meng Qingliang , Li Zhenbin , Peng Jiangyun , Liu Ying , Lu Min , Li Ming , Zhu Caifeng , Sun Yue , He Yanlin , Jin Yue , Gao Jingyue , Zhang Shumin , Li Peihao , Liao Rongjun , Liu Wei , Zhang Guoming
Published: January 2024

Background

In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule’s efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice.

Methods

This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators.

Results

Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group.

Conclusions

Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA.

Trial registration: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.