bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimisation of indole acetic acid production by Neopestalotiopsis aotearoa endophyte isolated from Thymus vulgaris and its impact on seed germination of Ocimum basilicum
Authors: Abdelhamid Sayeda A. , Abo Elsoud Mostafa M. , El-Baz A. F. , Nofal Ashraf M. , El-Banna Heba Y.
Published: July 2024

Background

Microbial growth during plant tissue culture is a common problem that causes significant losses in the plant micro-propagation system. Most of these endophytic microbes have the ability to propagate through horizontal and vertical transmission. On the one hand, these microbes provide a rich source of several beneficial metabolites.

Results

The present study reports on the isolation of fungal species from different in vitro medicinal plants (i.e., Breynia disticha major, Breynia disticha, Duranta plumieri, Thymus vulgaris, Salvia officinalis, Rosmarinus officinalis, and Ocimum basilicum l) cultures. These species were tested for their indole acetic acid (IAA) production capability. The most effective species for IAA production was that isolated from Thymus vulgaris plant (11.16 µg/mL) followed by that isolated from sweet basil plant (8.78 µg/mL). On screening for maximum IAA productivity, medium, “MOS + tryptophan” was chosen that gave 18.02 μg/mL. The macroscopic, microscopic examination and the 18S rRNA sequence analysis indicated that the isolate that given code T4 was identified as Neopestalotiopsis aotearoa (T4). The production of IAA by N. aotearoa was statistically modeled using the Box-Behnken design and optimized for maximum level, reaching 63.13 µg/mL. Also, IAA extract was administered to sweet basil seeds in vitro to determine its effect on plant growth traits. All concentrations of IAA extract boosted germination parameters as compared to controls, and 100 ppm of IAA extract exhibited a significant growth promotion effect for all seed germination measurements.

Conclusions

The IAA produced from N. aotearoa (T4) demonstrated an essential role in the enhancement of sweet basil (Ocimum basilicum) growth, suggesting that it can be employed to promote the plant development while lowering the deleterious effect of using synthetic compounds in the environment.
Measuring electronic health literacy in the context of diabetes care: psychometric evaluation of a Persian version of the condition-specific eHealth literacy scale for diabetes
Authors: Peimani Maryam , Tanhapour Mozhgan , Bandarian Fatemeh , Nasli-Esfahani Ensieh , Ostovar Afshin
Published: July 2024

Background

The rise of the internet and social media has led to increased interest among diabetes patients in using technology for information gathering and disease management. However, adequate eHealth literacy is crucial for protecting patients from unreliable diabetes-related information online.

Objective

To examine the psychometric characteristics and explore the preliminary validity of the Persian version of the Condition-specific eHealth Literacy Scale for Diabetes (Persian CeHLS-D) to assess eHealth literacy in the context of diabetes care.

Methods

After adapting, translating, examining content validity, and pilot testing the questionnaire, it was administered to 300 patients with type 2 diabetes mellitus (T2DM). Construct validity was assessed through confirmatory factor analysis, convergent and known-groups validity. The internal consistency (Cronbach’s alpha), composite reliability and maximum reliability, and test-retest correlation were assessed.

Results

Factor analysis supported the hypothesized two-factor model with 10 items, and the standardized factor loadings ranged from 0.44 to 0.86 (P-values < 0.001). Cronbach’s alpha and test-retest correlation were good for each factor. Convergent validity was confirmed by significant correlations of Persian CeHLS-D with diabetes health literacy, perceived usefulness and importance of using the internet for health information, internet anxiety, and perceived physical and mental health. Know-groups validity determined using groups with different internet-use frequencies, and different attitudes towards providing online healthcare services, were satisfied.

Conclusion

This study demonstrated the Persian CeHLS-D as a reliable and valid measure of eHealth literacy among patients with T2DM in Iran. Its satisfactory psychometric properties support its use in research and clinical settings to assess eHealth literacy and inform interventions.
Effects of a physical exercise programme on bodyweight, body condition score and chest, abdominal and thigh circumferences in dogs
Authors: Söder Josefin , Roman Erika , Berndtsson Johanna , Lindroth Katrin , Bergh Anna
Published: July 2024

Background

Research on the effects of physical exercise on canine body composition is limited. The aim of this study was to investigate the effects of a physical exercise programme on bodyweight, body condition score (BCS) and chest, abdominal and thigh circumferences in dogs. Twenty-one healthy dogs of different breeds exercised together with their owners during an eight-week programme consisting of jogging and strength exercises. Standardised measurements were performed in triplicates with a measuring tape on standing dogs. Chest circumference was measured at three anatomical locations, abdomen at two and thigh at one. Data on bodyweight, BCS (9-point scale) and circumferences were analysed with mixed model repeated measures analyses to evaluate changes after the programme and effects of target distance.

Results

Seven dog owners choose a target distance of 2 km and 14 owners choose 5–10 km. Mean BCS decreased (P = 0.007) after the programme (5.1 ± 0.9 vs. 4.7 ± 0.6) but there was no effect of target distance. Almost all chest and abdominal circumference measurements decreased (P ≤ 0.007) with the 2 km group driving the reduction in chest circumference and the 5–10 km group driving the reduction in abdominal circumference. In contrast, thigh circumference (28.8 ± 0.4 vs. 30.2 ± 0.4) increased (P = 0.007) while bodyweight was maintained. There were positive correlations between BCS and abdominal/chest ratios before and after the programme (Pearson correlation; R square ≤ 0.43, P ≤ 0.0012) but the mean ratio remained constant.

Conclusions

Results indicated a redistribution between total body fat and muscle mass in body composition of normal weight to slightly overweight dogs after the physical exercise programme. The use of bodyweight alone was not a reliable evaluation method to complement the BCS assessment. However, repeated measurements of chest, abdominal and thigh circumference might aid in the assessment of body composition in dogs performing physical exercise. Further research should include a control group and objective evaluations of total body fat and lean mass, in order to investigate the effectiveness of physical exercise as a freestanding method for decreasing BCS and increasing muscle mass in overweight dogs.
Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization
Authors: Zhao Jinxuan , Cheng Wei , Dai Yang , Li Yao , Feng Yuting , Tan Ying , Xue Qiucang , Bao Xue , Sun Xuan , Kang Lina , Mu Dan , Xu Biao
Published: July 2024

Background

Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.

Methods

Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.

Results

The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.

Conclusions

Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.
The potential of new nicotine and tobacco products as tools for people who smoke to quit combustible cigarettes – a systematic review of common practices and guidance towards a robust study protocol to measure cessation efficacy
Authors: Pluym Nikola , Burkhardt Therese , Scherer Gerhard , Scherer Max
Published: July 2024

New types of nicotine and tobacco products like electronic cigarettes (ECs), heated tobacco products or nicotine pouches have been discussed as less harmful alternatives to combustible cigarettes and other toxic forms of tobacco products. Their harm reduction potential lay in the efficient transition away from smoking to those new products. Numerous studies addressing the cessation efficacy of ECs have been published with contradictory outcomes. Yet, a comprehensive Cochrane review concluded with high certainty on the cessation efficacy of ECs. This prompted us to perform a review to identify weaknesses in common study designs and to summarize best practices for the study design on the potential of new nicotine products as cessation aids. 120 articles retrieved from Medline were found to be eligible. Most of the studies in the field were interventional trials while observational studies played a minor role in the evaluation of smoking cessation. Efficacy was predominantly assessed for ECs in 77% of the reports while heated tobacco (17%) and non-combustible products (11%) were less frequently investigated up to now. Measures to determine the efficacy were questionnaire-based assessments as well as use documentation/prevalence and abstinence rates. Studies varied largely in their duration and sample size with medians of 3 months and 156.5 participants, respectively.

With the help of this review, we identified several weaknesses in the common study designs. One major limitation in longitudinal trials was the lack of compliance measures suited to verify the use status over longer time periods, relying solely on self-reports. Moreover, the motivation of the participants to quit was rarely defined and a profound familiarization period was not taken into account for the majority of the studies. To what extent such weaknesses influence the outcome of the studies was beyond the scope of this review. We encourage researchers to consider the recommendations which resulted from this review in order to determine the abuse liability and cessation efficacy of the products in a more robust manner. Finally, we like to call attention to the missing data for low- and middle-income countries which would require quitting strategies most urgently to combat the tobacco smoking epidemic.
A taxonomy of demand-driven questions for use by evidence producers, intermediaries and decision-makers: results from a cross-sectional survey
Authors: Mansilla Cristián , Sweetman Arthur , Guyatt Gordon , Lavis John N.
Published: July 2024

Background

Globally, a growing number of calls to formalize and strengthen evidence-support systems have been released, all of which emphasize the importance of evidence-informed decision making. To achieve this, it is critical that evidence producers and decision-makers interact, and that decision-makers’ evidence needs can be efficiently translated into questions to which evidence producers can respond. This paper aims to create a taxonomy of demand-driven questions for use by evidence producers, intermediaries (i.e., people working in between researchers and decision-makers) and decision-makers.

Methods

We conducted a global cross-sectional survey of units providing some type of evidence support at the explicit request of decision-makers. Unit representatives were invited to answer an online questionnaire where they were asked to provide a list of the questions that they have addressed through their evidence-support mechanism. Descriptive analyses were used to analyze the survey responses, while the questions collected from each unit were iteratively analyzed to create a mutually exclusive and collectively exhaustive list of types of questions that can be answered with some form of evidence.

Results

Twenty-nine individuals completed the questionnaire, and more than 250 submitted questions were analysed to create a taxonomy of 41 different types of demand-driven questions. These 41 questions were organized by the goal to be achieved, and the goals were grouped in the four decision-making stages (i) clarifying a societal problem, its causes and potential impacts; (ii) finding and selecting options to address a problem; (iii) implementing or scaling-up an option; and (iv) monitoring implementation and evaluating impacts.

Conclusion

The mutually exclusive and collectively exhaustive list of demand-driven questions will help decision-makers (to ask and prioritize questions), evidence producers (to organize and present their work), and evidence-intermediaries (to connect evidence needs with evidence supply).
The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm
Authors: Vo Thi Thuy Tien , Peng Tzu-Yu , Nguyen Thi Hong , Bui Trang Ngoc Huyen , Wang Ching-Shuen , Lee Wei-Ju , Chen Yuh-Lien , Wu Yang-Che , Lee I-Ta
Published: July 2024

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.
Urinary microbiome dysbiosis is associated with an inflammatory environment and perturbed fatty acids metabolism in the pathogenesis of bladder cancer
Authors: Wu Cen , Wei Xiaoyu , Huang Zhiyang , Zheng Zhixiong , Zhang Wei , Chen Jiajun , Hong Hongchang , Li Weili
Published: July 2024

Background

Bladder cancer is a common malignancy with high recurrence rate. Early diagnosis and recurrence surveillance are pivotal to patients’ outcomes, which require novel minimal-invasive diagnostic tools. The urinary microbiome is associated with bladder cancer and can be used as biomarkers, but the underlying mechanism is to be fully illustrated and diagnostic performance to be improved.

Methods

A total of 23 treatment-naïve bladder cancer patients and 9 non-cancerous subjects were enrolled into the Before group and Control group. After surgery, 10 patients from the Before group were further assigned into After group. Void mid-stream urine samples were collected and sent for 16S rDNA sequencing, targeted metabolomic profiling, and flow cytometry. Next, correlations were analyzed between microbiota, metabolites, and cytokines. Finally, receiver operating characteristic (ROC) curves of the urinary biomarkers were plotted and compared.

Results

Comparing to the Control group, levels of IL-6 (p < 0.01), IL-8 (p < 0.05), and IL-10 (p < 0.05) were remarkably elevated in the Before group. The α diversity of urine microbiome was also significantly higher, with the feature microbiota positively correlated to the level of IL-6 (r = 0.58, p < 0.01). Significant differences in metabolic composition were also observed between the Before and Control groups, with fatty acids and fatty acylcarnitines enriched in the Before group. After tumor resection, cytokine levels and the overall microbiome structure in the After group remained similar to that of the Before group, but fatty acylcarnitines were significantly reduced (p < 0.05). Pathway enrichment analysis revealed beta-oxidation of fatty acids was significantly involved (p < 0.001). ROC curves showed that the biomarker panel of Actinomycetaceae + arachidonic acid + IL-6 had superior diagnostic performance, with sensitivity of 0.94 and specificity of 1.00.

Conclusions

Microbiome dysbiosis, proinflammatory environment and altered fatty acids metabolism are involved in the pathogenesis of bladder cancer, which may throw light on novel noninvasive diagnostic tool development.
Deep migration learning-based recognition of diseases and insect pests in Yunnan tea under complex environments
Authors: Li Zhaowen , Sun Jihong , Shen Yingming , Yang Ying , Wang Xijin , Wang Xinrui , Tian Peng , Qian Ye
Published: July 2024

Background

The occurrence, development, and outbreak of tea diseases and pests pose a significant challenge to the quality and yield of tea, necessitating prompt identification and control measures. Given the vast array of tea diseases and pests, coupled with the intricacies of the tea planting environment, accurate and rapid diagnosis remains elusive. In addressing this issue, the present study investigates the utilization of transfer learning convolution neural networks for the identification of tea diseases and pests. Our objective is to facilitate the accurate and expeditious detection of diseases and pests affecting the Yunnan Big leaf kind of tea within its complex ecological niche.

Results

Initially, we gathered 1878 image data encompassing 10 prevalent types of tea diseases and pests from complex environments within tea plantations, compiling a comprehensive dataset. Additionally, we employed data augmentation techniques to enrich the sample diversity. Leveraging the ImageNet pre-trained model, we conducted a comprehensive evaluation and identified the Xception architecture as the most effective model. Notably, the integration of an attention mechanism within the Xeption model did not yield improvements in recognition performance. Subsequently, through transfer learning and the freezing core strategy, we achieved a test accuracy rate of 98.58% and a verification accuracy rate of 98.2310%.

Conclusions

These outcomes signify a significant stride towards accurate and timely detection, holding promise for enhancing the sustainability and productivity of Yunnan tea. Our findings provide a theoretical foundation and technical guidance for the development of online detection technologies for tea diseases and pests in Yunnan.
Which one is the best in treating deep venous thrombosis —— percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?
Authors: Zhang Hao , Li Xiao-ye , Li Jia-si , Xia Shi-bo , Song Chao , Lu Qing-sheng , Zhao Wei , Zhang Lei
Published: July 2024

Objective

To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both.

Methods

One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up.

Results

Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006).

Conclusion

Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.
Connect-ROD – development and qualitative evaluation of a community-based group intervention to support well-being in patients with a rare or orphan disease
Authors: Bardon Cécile , Rioux Marie-Éve , Rivard Mélina , Viquez Porras Floryana-Maria , Zaky Julie
Published: July 2024

Background

Patients living with various rare or orphan diseases (ROD) experience common psychosocial difficulties. Those need emerge from a combination of factors, such as the large variety of patients and the rarity of resources, as well as concentrated efforts on physical health needs that yielded increases in life expectancy and quality in patients. A gap is therefore rising in the consideration of psychosocial needs of patients, such as coping with the impacts of physical limitations, reducing social isolation and distress. To contribute to address this gap, we developed, pilot-tested and evaluated the acceptability, feasibility, implementation, and short-term effects of Connect-ROD, an online group intervention to support adult patients with a ROD (AP-ROD), which aims to improve coping mechanisms, reinforce sense of control, and support personal goals of AP-ROD.

A qualitative study comprising of in-depth pretests, post-test interviews and standardized questionnaires, was conducted with 14 participants in two consecutive intervention groups.

Results

The Connect-ROD intervention is strongly anchored in acceptance and commitment therapy as well as community psychology approaches. A pilot test allowed us to improve on the initial structure and to produce a manualized 10-week program delivered online, made up of 2-h sessions comprising formal activities, exchanges and homework. The evaluation showed satisfactory acceptability and accessibility, compliant delivery by facilitators, and promising short-term effects on personal objectives, sense of control, coping mechanisms, symptom management, acceptance of the emotions associated with the disease, distress, self-efficacy, social support and connectedness. The program did not show short-term effects on overall quality of life.

Conclusion

It is recommended that Connect-ROD is evaluated on a larger scale. It seems promising to support various AP-ROD who live with the complex psychosocial consequences of their disease.
lncRNA FGD5-AS1 is required for gastric cancer proliferation by inhibiting cell senescence and ROS production via stabilizing YBX1
Authors: Qin Shanshan , Liu Yue , Zhang Xiangang , Huang Pan , Xia Lingyun , Leng Weidong , Li Dandan
Published: July 2024

Background

The vast majority of lncRNAs have low expression abundance, which greatly limits their functional range and impact. As a high expression abundance lncRNA, FGD5-AS1’s non-ceRNA biological function in cancer is unclear.

Methods

RNA-seq studies and chromatin immunoprecipitation (Chip) assays were performed to identify ZEB1-regulated lncRNAs. RNA sequencing, RNA pulldown, RNA Immunoprecipitation assays, and rescue assays were conducted to explore the molecular mechanisms of FGD5-AS1 in GC.

Results

As one of the most abundant lncRNAs in cells, FGD5-AS1 has been shown to be transcriptionally activated by ZEB1, thus closely related to epithelial-mesenchymal transition (EMT) signaling. Clinical analysis showed that FGD5-AS1 overexpression was clinically associated with lymph node metastasis, and predicted poor survival in GC. Loss-of-function studies confirmed that FGD5-AS1 knockdown inhibited GC proliferation and induced cisplatin chemosensibility, cell senescence, and DNA damage in GC cells. Mechanismically, FGD5-AS1 is a YBX1-binding lncRNA due to its mRNA contains three adjacent structural motifs (UAAUCCCA, ACCAGCCU, and CAGUGAGC) that can be recognized and bound by YBX1. And this RNA-protein interaction prolonged the half-life of the YBX1 protein in GC. Additionally, a rescue assay showed that FGD5-AS1 promotes GC by repressing cell senescence and ROS production via YBX1.

Conclusion

FGD5-AS1 is a cellular high-abundant lncRNA that is transcriptionally regulated by ZEB1. FGD5-AS1 overexpression promoted GC progression by inhibiting cell senescence and ROS production through binding and stabilizing the YBX1 protein.
Role of central endpoint adjudication and challenges in trials on neonatal sepsis—a case of ProSPoNS trial
Authors: Sinha Anju Pradhan , Raja Dilip , Mahajan Kamlesh S. , Sharma Piyu , Gupta Subodh S. , Poluru Ramesh , Kawade Anand S. , Dayma Girish , Sazawal Sunil , Bavdekar Ashish , Parida Sailajanandan , Nangia Sushma , Raut Abhishek V. , Bethou Adhisivam , Devi Prabhabati , Gorpade Makrand , Fatima Tharika , Nayak Rashmita , Kapil Arti , Azam Mohd. , Khan Pearlin A. , Pandey Ravindra Mohan , Arora Narendra Kumar ,   ProSPoNS Study Group, Prajapati Dixit , Mathur Apoorva , Gupta Pankaj , Kumari Payal
Published: July 2024

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on “sepsis,” the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the “physician diagnosed sepsis.” To align all the three above, the investigators meeting, held on 17th–18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that “physician diagnosed sepsis” is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine “physician diagnosed sepsis”: (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.

Trial registration

Clinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.
scMultiome analysis identifies a single caudal hindbrain compartment in the developing zebrafish nervous system
Authors: Warns Jessica , Kim Yong-II , O’Rourke Rebecca , Sagerström Charles G.
Published: July 2024

Background

A key step in nervous system development involves the coordinated control of neural progenitor specification and positioning. A long-standing model for the vertebrate CNS postulates that transient anatomical compartments – known as neuromeres – function to position neural progenitors along the embryonic anteroposterior neuraxis. Such neuromeres are apparent in the embryonic hindbrain – that contains six rhombomeres with morphologically apparent boundaries – but other neuromeres lack clear morphological boundaries and have instead been defined by different criteria, such as differences in gene expression patterns and the outcomes of transplantation experiments. Accordingly, the caudal hindbrain (CHB) posterior to rhombomere (r) 6 has been variably proposed to contain from two to five ‘pseudo-rhombomeres’, but the lack of comprehensive molecular data has precluded a detailed definition of such structures.

Methods

We used single-cell Multiome analysis, which allows simultaneous characterization of gene expression and chromatin state of individual cell nuclei, to identify and characterize CHB progenitors in the developing zebrafish CNS.

Results

We identified CHB progenitors as a transcriptionally distinct population, that also possesses a unique profile of accessible transcription factor binding motifs, relative to both r6 and the spinal cord. This CHB population can be subdivided along its dorsoventral axis based on molecular characteristics, but we do not find any molecular evidence that it contains multiple pseudo-rhombomeres. We further observe that the CHB is closely related to r6 at the earliest embryonic stages, but becomes more divergent over time, and that it is defined by a unique gene regulatory network.

Conclusions

We conclude that the early CHB represents a single neuromere compartment that cannot be molecularly subdivided into pseudo-rhombomeres and that it may share an embryonic origin with r6.
Association of thrombotic microangiopathy with interferon therapy for hepatitis B: a case report
Authors: Wei Shan , Mei Wenjuan , Wang Ying
Published: July 2024

Background

Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy.

Case presentation

We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient’s renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable.

Conclusions

This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency.
Determinants of mortality status and population attributable risk fractions of the North West Province, South African site of the international PURE study
Authors: Ricci Cristian , Kruger Iolanthe M. , Kruger Herculina S. , Breet Yolandi , Moss Sarah J. , van Oort Abie , Bester Petra , Pieters Marlien
Published: July 2024

Background

Mortality data and comparative risk assessments from sub-Saharan Africa are limited. There is an urgent need for high quality population health surveys to be conducted, to improve the national health surveillance system. Our aim was to perform a comparative risk assesment and report on the mortality status and cause of death data of participants from a South African site of the international Prospective Urban Rural Epidemiology study.

Methods

1 921 Black participants were included, with a median observational time of 13 years resulting in 21 525 person-years. We performed a comparative risk assessment considering four health status domains: locality (rural vs. urban), socio-economic status (SES) (education and employment), lifestyle factors (physical activity, smoking and alcohol consumption) and prevalent diseases (human immunodeficiency virus (HIV), type 2 diabetes mellitus and hypertension). Next, population-attributable fractions (PAFs) were calculated to determine the mortality risk attributable to modifiable determinants.

Results

577 all-cause deaths occurred. Infectious diseases (28.1% of all deaths) were the most frequent cause of death, followed by cardiovascular disease (CVD) (22.4%), respiratory diseases (11.6%) and cancer (11.1%). The three main contributors to all-cause mortality were HIV infection, high SES and being underweight. HIV infection and underweight were the main contributors to infectious disease mortality and hypertension, the urban environment, and physical inactivity to CVD mortality. HIV had the highest PAF, followed by physical inactivity, alcohol and tobacco use and hypertension (for CVD mortality).

Conclusion

This African population suffers from a quadruple burden of disease. Urban locality, high SES, prevalent disease (HIV and hypertension) and lifestyle factors (physical inactivity, tobacco and alcohol use) all contributed in varying degrees to all-cause and cause-specific mortalities. Our data confirm the public health importance of addressing HIV and hypertension, but also highlights the importance of physical inactivity, tobacco use and alcohol consumption as focal points for public health strategies to produce the most efficient mortality reduction outcomes.
Secondary attack rate following on-site isolation of patients with suspected COVID-19 in multiple-bed rooms
Authors: Ragozzino Silvio , Kuehl Richard , Leuzinger Karoline , Schläpfer Pascal , Urwyler Pascal , Durovic Ana , Zingg Sandra , von Rotz Matthias , Battegay Manuel , Widmer Andreas F , Hirsch Hans H , Bassetti Stefano , Tschudin-Sutter Sarah
Published: July 2024

The implementation of isolation precautions for patients with suspected Coronavirus Disease 2019 (COVID-19) and pending test results is resource intensive. Due to the limited availability of single-bed rooms at our institution, we isolated patients with suspected COVID-19 together with patients without suspected COVID-19 on-site in multiple-bed rooms until SARS-CoV-2-test results were available. We evaluated the likelihood of SARS-CoV-2 transmission to individuals sharing the room with patients isolated on-site. This observational study was performed at the University Hospital Basel, Switzerland, from 03/20 − 11/20. Secondary attack rates were compared between patients hospitalized in multiple-bed rooms and exposed to individuals subjected to on-site isolation precautions (on-site isolation group), and patients exposed to individuals initially not identified as having COVID-19, and not placed under isolation precautions until the diagnosis was suspected (control group). Transmission events were confirmed by whole-genome sequencing. Among 1,218 patients with suspected COVID-19, 67 (5.5%) tested positive for SARS-CoV-2. Of these, 21 were isolated on-site potentially exposing 27 patients sharing the same room. Median contact time was 12 h (interquartile range 7–18 h). SARS-CoV-2 transmission was identified in none of the patients in the on-site isolation group vs. 10/63 (15.9%) in the control group (p = 0.03). Isolation on-site of suspected COVID-19-patients in multiple-bed rooms avoided single-room occupancy and subsequent in-hospital relocation for many patients without confirmed SARS-CoV-2-infection. The absence of secondary transmission among the exposed patients in the on-site isolation group allows for assessment of the risk/benefit ratio of this strategy given the limitation of a small sample size.
Inclinometer use in primary total hip arthroplasty does not improve acetabular component positioning: a non-randomized control trial
Authors: Goldstein Kyle , Tyndall Wyatt , Nickol Michaela E. , van der Merwe Johannes M.
Published: July 2024

Introduction

Total hip arthroplasty (THA) is a common surgical procedure that aims to relieve pain, improve function, and increase mobility in patients with hip joint pathology. One of the most challenging aspects of THA is to determine the correct angle of the acetabular component’s placement. Intraoperative inclinometers have emerged as a promising tool to obtain accurate measurements of the acetabular component’s inclination. The primary objective of this study was to evaluate the accuracy and efficacy of using intraoperative inclinometers for THA.

Methods

This non-randomized control trial evaluated patients undergoing primary THA. Patients in the inclinometer group had an inclinometer used intraoperatively to measure acetabular component inclination, and patients in the control group had no inclinometer. Inclination and anteversion of the acetabular component were measured on postoperative radiographs.

Results

A total of 223 patients were included in the study. The mean inclination angle of the acetabular cup was significantly higher in the inclinometer group (43.9° vs. 41.5°, P < 0.001). This difference was not clinically significant. There was no significant difference in anteversion. There were no significant differences in the number of patients within the safe zones for inclination or anteversion, or in the number of patients experiencing a dislocation. No correlation was found between inclinometer measurement and measured acetabular component inclination. Inclinometer use and body mass index (BMI) were the sole statistically significant factors in determining acetabular component inclination.

Conclusions

This study indicated no current benefit to inclinometer use during primary THA, as measured by inclination, anteversion, and dislocation rate. However, this might be confounded by subtle variations in patient positioning, which may be a strong area of study in the future.
Serum mir-31-5p is a reliable biomarker in patients with oral squamous cell carcinoma and oral lichen planus
Authors: Mohtasham Nooshin , Ghorbani Zahra , Ayatollahi Hossein , Arab Fatemeh , Aghaee-Bakhtiari Seyed Hamid , Rasoulian Bashir , Mohajertehran Farnaz
Published: July 2024

Background

MicroRNAs have been proposed as a novel regulatory biomarker for gene expression and early diagnosis of cancers. In this study, we evaluate the expression level of miR-31-5p in the serum of patients with oral squamous cell carcinoma, oral lichen planus, and a healthy control group to obtain a primary diagnostic biomarker.

Materials and methods

Serum was collected from patients with oral lichen planus (n = 32), patients with oral squamous cell carcinoma (n = 35), and healthy subjects (n = 32). MicroRNA was isolated from serum and cDNA was made from it. Then, the quantitative and qualitative expression of miR-31-5p levels among the samples was checked by the qRT-PCR method.

Results

In this study, three groups were quantitatively and qualitatively analyzed for miR-31-5p expression in serum. The results showed that there was a statistically significant correlation between the mean quantitative and qualitative expression of miR-31-5p among the three groups (P < 0.05).

Conclusions

The expression of miR-31-5p was significantly higher in patients with oral squamous cell carcinoma and oral lichen planus compared with healthy controls. MiR-31-5p can be considered as a biomarker in serum that could be potentially reliable in the diagnosis and prognosis of oral squamous cell carcinoma and also in the transformation of lichen planus.
Efficient pure qP-wave modeling and reverse time migration in tilted transversely isotropic media calculated by a finite-difference approach
Authors: Mao Qiang , Huang Jianping , Mu Xinru , Zhang Yujian
Published: July 2024

Subsurface anisotropy is commonly induced by shale layers, aligned cracks, and fine bedding and has a significant impact on seismic wave propagation. Ignoring anisotropic effects during seismic migration degrades image quality. Therefore, we derive a pure qP-wave equation with high accuracy for modeling seismic wave propagation in tilted transversely isotropic (TTI) media. However, the derived pure qP-wave equation requires a computationally expensive spectral-based method for performing numerical simulations. This is unsuitable for large-scale industrial applications, particularly 3D applications. For numerical efficiency, we first decompose the newly derived wave equation into some fractional differential operators and spatial derivatives. The spatial derivatives can be directly solved by conventional finite-difference (FD) approaches. Then, we use an asymptotic approximation to find an equivalent form of fractional differential operators, obtaining scalar operators that we can discretize with the FD method. Numerical tests show that our TTI pure qP-wave equation with an FD discretization can produce accurate and highly efficient wavefield simulations in TTI media. We also use our TTI pure qP-wave equation with an FD discretization as a forward engine to implement TTI reverse time migration (RTM). Synthetic examples and a field data test demonstrate that our TTI RTM can effectively correct the anisotropic effects, providing high-quality imaging results while maintaining good computational efficiency.
The design, preclinical study and phase I dose escalation plan of a HER2 targeted immunoliposome (HF-K1) for HER2 low solid tumor treatment.
Authors: Jin Shanshan , Zhang Xiaochen , Jia Yunlu , Dai Yongchao , Xu Fengwei , Huang Yongfeng , Wang Xun , Wu Hailong , Shao Yu , Long Jinfeng , Zheng Anjie , Xu Yuhong
Published: July 2024

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Background: Doxorubicin liposome formulations are being used extensively in the clinic in anthracycline chemotherapy with reduced cardiotoxicity. However, they did not improve clinical outcome because the cancer cell uptake of PEG-coated liposomes is poor. So, the concept of coating antibodies on the liposome surface was initiated and they were named immunoliposomes. There have been numerous studies conducted world-wide for the development of immunoliposomes but none have progressed to late-stage development. Our work draws on the experiences of these prior studies with a new perspective. Since the mechanism of immunoliposomes is similar to those of ADCs, we sought to compare immunoliposomes with ADCs containing the same cancer cell binding domain, for target cell binding capability, binding affinity as well as in vivo distribution, tumor tissue accumulation, and anti-tumor activities. The lessons learned from the success of many ADC products may be applicable to the development of immunoliposomes. Methods: The antibody to liposome ratio (ALR) and the drug to lipid ratio (DLR) of the immunoliposomes were selected by in vitro and in vivo anti-cancer activity screening. Cell lines with different HER2 expression levels were used to study immunoliposome binding, cell uptake, drug delivery and cytotoxicity. PK, drug distribution, efficacy and toxicities studies were conducted in respective CDX and PDX mice and non-rodent models. Based on these studies, a phase I dose escalation study plan was designed and the study is now ongoing. Results: HF-K1 was designed to have an average of 10 anti-HER2 Fab on each liposome surface and approximately 2300 doxorubicin molecules inside. The equivalent drug to antibody ratio (DAR) is 230. HF-K1 can bind to cancer cells with different levels of HER2 expression with similar kinetics and induces cells death at IC50s of 0.35-6.46 μg/ml Fab concentration. It has a long circulation behavior and enhanced permeability and retention (EPR) in tumor tissues. The clearance T1/2 of HF-K1 in mice and monkey is 12.78 h and 47.12 h, respectively. Evaluation of HF-K1 activity in vivo showed significant tumor growth inhibition >95% at the equivalent antibody dose of 3.6 mg/kg in various mouse tumor models including HER2 low and HER2 very low (HER2-). Similar activities were shown by ADCs including T-DM1 and DS-8201a at about 10 mg/kg. Conclusions: The encouraging preclinical data supported a clinical trial starting with dose escalation at equivalent antibody doses of 0.72 mg/m2, 2.16 mg/m2, 5.4 mg/m2, 10.8 mg/m2, 16.2 mg/m2, and 21.6 mg/m2. The study is ongoing to determine the safety, tolerability, PK, and preliminary antitumor efficacy in participants with HER2 positive or HER2 low expression advanced solid tumors (NCT05861895). Clinical trial information: NCT05861895 .
Maximal acceleration in Rainbow gravity
Authors: R Bhagya. , Sreekumar Harsha , Panja Suman Kumar
Published: July 2024

In this paper, we derive maximal acceleration of a massive particle in Rainbow gravity. Using eight-dimensional phase-space metric compatible with Rainbow gravity, we obtain the maximal acceleration, valid up to first order in the Rainbow gravity parameter η. Using the positivity condition on maximal acceleration, we find that the upper bound on the Rainbow gravity parameter is of the order of

for positron and

for a black hole. After obtaining the expression for maximal acceleration for different choices of Rainbow functions, we derive corresponding modifications to Unruh temperature. Comparing with the observational value of the Unruh temperature, we find the upper bound on η as

for positron radiation. We then derive geodesic equations for different choices of Rainbow functions and also obtain the Newtonian limit of these geodesic equations. We find that the changes in the value of maximum acceleration, maximum temperature and Newtonian force equation are dependent on the choices of Rainbow functions.