bluuebunny/crossref_metadata_2025 huggingface dataset:
Butyrate induces higher host transcriptional changes to inhibit porcine epidemic diarrhea virus strain CV777 infection in porcine intestine epithelial cells
Authors: Zhong Zhen , Zhang Yaqin , Zhao Xuting , Zhou Chunbao , Zhu Shubin , Wu Jiayun
Published: July 2024

Newborn piglets’ health is seriously threatened by the porcine epidemic diarrhea virus (PEDV), which also has a significant effect on the pig industry. The gut microbiota produces butyrate, an abundant metabolite that modulates intestinal function through many methods to improve immunological and intestinal barrier function. The objective of this investigation was to ascertain how elevated butyrate concentrations impacted the host transcriptional profile of PEDV CV777 strain infection. Our findings showed that higher concentrations of butyrate have a stronger inhibitory effect on PEDV CV777 strain infection. According to RNA-seq data, higher concentrations of butyrate induced more significant transcriptional changes in IPEC-J2 cells, and signaling pathways such as PI3K-AKT may play a role in the inhibition of PEDV CV777 strain by high concentrations of butyrate. Ultimately, we offer a theoretical and experimental framework for future research and development of novel approaches to harness butyrate’s antiviral infection properties.
Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens
Authors: Xue Li , Zhu Jianhong , Lei Ke , Liu Zeshi , Tang Yiwei , Zhong Bo , Gao Ning , Xiong Chaoliang , Lei Jing , Tian Ying , Zhou Weixiao , Feng Nan , Zhang Xue , Chen Dong , Li Jing , Geng Yan
Published: July 2024

Objectives

The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed.

Methods

Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method.

Results

The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively.

Conclusions

The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.
Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion
Authors: Qiu Shikang , Wang Qiannan , Jiang Huihui , Feng Limin
Published: July 2024

Background

Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN.

Methods

IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1–2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers.

Results

The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker.

Conclusions

Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.
Methods of muscle spasticity assessment in children with cerebral palsy: a scoping review
Authors: Nourizadeh Mehdi , Shadgan Babak , Abbasidezfouli Samin , Juricic Maria , Mulpuri Kishore
Published: July 2024

Background

Evaluating muscle spasticity in children with cerebral palsy (CP) is essential for determining the most effective treatment strategies. This scoping review assesses the current methods used to evaluate muscle spasticity, highlighting both traditional and innovative technologies, and their respective advantages and limitations.

Methods

A search (to April 2024) used keywords such as muscle spasticity, cerebral palsy, and assessment methods. Selection criteria included articles involving CP children, assessing spasticity objectively/subjectively, comparing methods, or evaluating method effectiveness.

Results

From an initial pool of 1971 articles, 30 met our inclusion criteria. These studies collectively appraised a variety of techniques ranging from well-established clinical scales like the modified Ashworth Scale and Tardieu Scale, to cutting-edge technologies such as real-time sonoelastography and inertial sensors. Notably, innovative methods such as the dynamic evaluation of range of motion scale and the stiffness tool were highlighted for their potential to provide more nuanced and precise assessments of spasticity. The review unveiled a critical insight: while traditional methods are convenient and widely used, they often fall short in reliability and objectivity.

Conclusion

The review discussed the strengths and limitations of each method and concluded that more reliable methods are needed to measure the level of muscle spasticity more accurately.
Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study
Authors: Yang Kai-Lin , Yen Ting-An , Lin Fang-Ju , Hsu Chien-Ning , Wang Chi-Chuan
Published: July 2024

Background

The gut microbiota is believed to influence neurodevelopment through the gut–brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD.

Methods

This was a retrospective cohort study using 2003–2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk.

Results

The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01–1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90–0.94).

Conclusions

The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.
Discovery of pararealgar and semi-amorphous pararealgar in Rembrandt's The Night Watch: analytical study and historical contextualization
Authors: De Keyser Nouchka , Broers Fréderique T. H. , Vanmeert Frederik , van Loon Annelies , Gabrieli Francesca , De Meyer Steven , Gestels Arthur , Gonzalez Victor , Hermens Erma , Noble Petria , Meirer Florian , Janssens Koen , Keune Katrien
Published: July 2024

This article reports on the discovery of pararealgar and semi-amorphous pararealgar in Rembrandt's masterpiece The Night Watch. A large-scale research project named Operation Night Watch was started in 2019. A variety of non-invasive analytical imaging techniques, together with paint sample research, has provided new information about Rembrandt's pigments, materials, and techniques as well as the current condition of the painting. Macroscopic X-ray fluorescence, macroscopic X-ray powder diffraction and reflectance imaging spectroscopy identified the presence of arsenic sulfide pigments and degradation products of these pigments in the doublet sleeves and embroidered buff coat worn by Lieutenant Willem van Ruytenburch (central figure to the right of Captain Frans Banninck Cocq). Examination by light microscopy of two paint samples taken from this area shows a mixture of large sharp-edged tabular yellow and orange to red pigment particles, and scanning electron microscopy-energy dispersive X-ray analysis identified these particles as containing arsenic and sulfur. Using micro-Raman spectroscopy, the yellow particles were identified as pararealgar, and the orange to red particles as semi-amorphous pararealgar. Synchrotron-based X-ray diffraction allowed visualization of the presence of multiple degradation products associated with arsenic sulfides throughout the paint layer. The discovery of pararealgar and semi-amorphous pararealgar is a new addition to Rembrandt's pigment palette. To contextualize our findings and to hypothesize why, how, and where Rembrandt obtained the pigments, we studied related historical sources. A comprehensive review of historical sources gives insight into the types of artificial arsenic sulfides that were available and suggests that a broader range of arsenic pigments could have been available in Amsterdam in the seventeenth century than previously thought. This is supported by the use of a very similar mixture of pigments by Willem Kalf (1619–1693), a contemporary artist based in Amsterdam. Together with the condition of the particles in the paint cross sections, this brings us to the conclusion that Rembrandt intentionally used pararealgar and semi-amorphous pararealgar, together with lead–tin yellow and vermilion, to create an orange paint.
Pediatric injuries and poisonings associated with detergent packets: results from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), 2011–2023
Authors: Zutrauen Sarah , Cheesman James , McFaull Steven R.
Published: July 2024

Background

Detergent packets are common household products; however, they pose a risk of injuries and poisonings, especially among children. This study examined the epidemiological characteristics of pediatric injuries and poisonings related to all types of detergent packets in Canada using emergency department (ED) data from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) database.

Methods

The CHIRPP database was searched for ED visit records for injuries and poisonings related to all types of detergent packets between April 1, 2011 and October 12, 2023 (N = 2,021,814) using variable codes and narratives. Data for individuals aged 17 years and younger were analyzed descriptively. Temporal trends in the number of detergent packet-related injuries and poisonings per 100,000 CHIRPP cases were assessed using Joinpoint regression and annual percent change (APC). A proportion ratio and 95% confidence intervals (CI) were calculated to compare the proportion of detergent packet-related cases in CHIRPP during two 34-months periods, pre-COVID-19 pandemic and after the beginning of the pandemic.

Results

There were 904 detergent packet-related cases among children and youth aged 17 years and younger identified in CHIRPP between April 1, 2011 and October 12, 2023, representing 59.9 cases per 100,000 CHIRPP cases. The majority (86.5%) of cases were among children aged 4 years and younger. Poisonings (58.8%) and eye injuries (30.6%) were the most frequent primary diagnoses. Unintentional ingestion (56.9%) and squeezing/breaking a detergent packet (32.3%) were the most frequent exposure mechanisms. Sixty-five patients (7.2%) were admitted to hospital. The number of detergent packet-related cases per 100,000 CHIRPP cases increased by 5.0% (95% CI 0.8, 10.2) annually between 2012 and 2022. The number of detergent packet-related poisonings per 100,000 CHIRPP cases decreased by 15.3% (95% CI − 22.3, − 10.6) annually between 2015 and 2022, whereas eye injuries showed an average annual percent increase of 16.6% (95% CI 11.2, 23.0) between 2012 and 2022. The proportion of detergent packet-related cases in CHIRPP after the beginning of the pandemic (79.9/100,000 CHIRPP cases) was 1.43 (95% CI 1.20, 1.71) times greater than pre-pandemic (55.7/100,000 CHIRPP cases).

Conclusions

Detergent packet-related injuries and poisonings are a persisting issue. Continued surveillance and prevention efforts are needed to reduce detergent packet-related injuries and poisonings in Canada, particularly among children and youth.
DCE-MRI to distinguish all monoclonal plasma cell disease stages and correlation with diffusion-weighted MRI/PET-based biomarkers in a hybrid simultaneous whole body-2-[18F]FDG-PET/MRI imaging approach
Authors: Jamet Bastien , Necib Hatem , Carlier Thomas , Frampas Eric , Bazin Juliette , Desfontis Paul-Henri , Monnet Aurélien , Bodet-Milin Caroline , Moreau Philippe , Touzeau Cyrille , Kraeber-Bodere Francoise
Published: July 2024

Background

Dynamic contrast-enhanced-MRI (DCE-MRI) is able to study bone marrow angiogenesis in patients with multiple myeloma (MM) and asymptomatic precursor diseases but its role in the management of MM has not yet been established. The aims of this prospective study was to compare DCE-MRI-based parameters between all monoclonal plasma cell disease stages in order to find out discriminatory parameters and to seek correlations with other diffusion-weighted MRI and positron emission tomography (PET)-based biomarkers in a hybrid simultaneous whole-body-2-[18F]fluorodeoxyglucose (FDG)-PET/MRI (WB-2-[18F]FDG-PET/MRI) imaging approach.

Methods

Patients with newly diagnosed Monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or symptomatic MM according to international myeloma working group and underwent WB-2-[18F]FDG-PET/MRI imaging including bone marrow DCE sequences at the Nantes University Hospital were prospectively enrolled in this study before receiving treatment.

Results

One hundred and sixty-seven patients (N = 167, mean age: 64 years ± 11 [Standard deviation], 66 males) were considered for the analysis. DCE-MRI-based Peak Enhancement Intensity (PEI), Time to PEI (TPEI) and their maximum intensity time ratio (MITR: PEI/TPEI) values were significantly different between the different monoclonal plasma cell disease stages, PEI values increasing and TPEI values decreasing progressively along the spectrum of plasma cell disorders, from MGUS stage to symptomatic multiple myeloma. PEI values were significantly higher in patients with diffuse bone marrow involvement (either in PET or in MRI images) than in those without diffuse bone marrow involvement, unlike TPEI values. PEI and TPEI values were not significantly different between patients with or without focal bone lesions.

Conclusion

Different DCE-MRI-based parameters (PEI, TPEI, MITR) could significantly differentiate all monoclonal plasma cell disease stages and complemented conventional MRI and PET-based biomarkers.
Noneffectiveness of cryostorage duration on clinical and neonatal outcomes after single vitrified-warmed blastocyst transfers
Authors: Baatarsuren Mungunshagai , Jamiyansuren Jambaldorj , Ganbaatar Chinzorig , Sengebaljir Davaakhuu , Erdenekhuyag Belguune , Enkhbaatar Sandag , Mungunsuvd Namsrai , Baljinnyam Lkhagvasuren , Tumur-Ochir Ganjiguur , Amarsaikhan Ariunaa , Dorjpurev Amarjargal , Ganbat Gereltsetseg , Boris Tsogzolmaa , Khangarid Azjargal
Published: July 2024

Background

In the current era of assisted reproductive technology, the strategy of single vitrified-warmed blastocyst transfer (SVBT) is acknowledged for positively impacting clinical outcomes and preventing the risk of multiple conceptions. Previous studies have indicated that blastocyst grade and the day of blastocyst positively correlate with outcomes. Moreover, storage duration has no significant effect on survival rates, clinical outcomes, and neonatal outcomes. However, some researchers express controversial opinions on cryostorage duration, and their findings suggest a negative impact on clinical outcomes. These results remain subject to controversy, and limited studies exist regarding the outcomes after SVBT. Therefore, our study aims to investigate the impact of the day of blastocyst, blastocyst grade, and blastocyst cryostorage duration on clinical and neonatal outcomes following SVBT in patients who underwent clomiphene-citrate-based minimal stimulation.

Material and methods

In this study, retrospective cohort study data collected from June 2015 to April 2023 included 2107 patients with first SVBT cycles who underwent a clomiphene-based minimal ovarian stimulation protocol or a drug-free natural protocol at the Ojinmed IVF Center. Patients were categorized into four groups based on blastocyst cryostorage duration: group 1 (< 2 months, n = 882), group 2 (3–6 months, n = 794), group 3 (7–12 months, n = 187), group 4 (13–24 months, n = 126), and group 5 (25–81 months, n = 118). The patient’s clinical and neonatal outcomes were compared with cryostorage duration after the propensity score matched.

Result

Multivariable logistic regression analysis revealed that prolonged cryostorage duration insignificantly correlated with clinical outcomes. Additionally, neonatal outcomes are not correlated with cryostorage duration.

Conclusions

The patient must consider several parameters when selecting embryos for transfer, including the duration of cryostorage. Our study results show that for the first single vitrified-warmed blastocyst transfer of patients who underwent clomiphene citrate-based minimal stimulation, cryostorage duration does not affect outcomes.
A multicenter phase 1 trial of tucatinib, trastuzumab, and capecitabine with stereotactic radiosurgery in patients with brain metastases from HER-2–positive breast cancer (TUTOR).
Authors: Ahluwalia Manmeet Singh , Ozair Ahmad , Bardhan Mainak , Bellur Shreyas S , Perche Dilanis C. , Starosciak Amy K. , Leon-Ariza Daniel S. , Khosla Atulya Aman , Rubens Muni , Odia Yazmin , Mehta Minesh P. , Kotecha Rupesh , McDermott Michael W , Sandoval-Leon Ana Cristina , Mahtani Reshma L. , Peereboom David M.
Published: July 2024

TPS2089

Background: 20-40% of HER-2-positive breast cancer patients develop brain metastases (BMs), for which stereotactic radiosurgery (SRS) is used for local disease control. Tucatinib, an oral HER-2-selective tyrosine kinase inhibitor (TKI), has been demonstrated to be safe and efficacious in HER-2-positive breast cancer in combination with capecitabine and trastuzumab. The synergism between these three drugs and radiation may potentially enhance DNA damage, causing increased apoptosis. We hypothesize that this 3-drug therapy, in combination with SRS in patients with HER-2 positive breast cancer BM (BCBM), may be safe and provide superior long-term control of intracranial and systemic disease. Methods: This is a prospective, single-arm, multicenter, ongoing, phase 1 clinical trial. Patients aged 18-80 years, ECOG score 0-2, normal organ function, and up to 10 newly-diagnosed BMs is planned to enroll at six centers in the US. Any number of prior systemic therapies are allowed, except tucatinib and capecitabine. Key exclusion criteria include leptomeningeal metastases, evidence of intra-tumoral or peri-tumoral hemorrhage, and BMs within 5 mm of the optic chiasm/nerve. Patients receive oral tucatinib alongside SRS, followed by a two-week dose-limiting toxicity (DLT) period, and subsequently continue the regimen until disease progression or intolerable toxicity. DLTs are defined by Grade 3 or 4 thrombocytopenia, grade 4 anemia, grade 4 neutropenia lasting more than seven days, febrile neutropenia, and grade 3 non-hematologic toxicity. Primary study endpoint is maximum tolerated dose (MTD) of tucatinib in combinatorial therapy. This de-escalation study starts at 300 mg dose level (DL), with DL-1 250 mg, and DL-2 200 mg, based on a 3 + 3 design. Cohort expansion at MTD is planned to a total of 40 patients. Secondary endpoints include efficacy as determined by response rate, intracranial progression-free survival (PFS), extracranial PFS, overall survival, quality of life as assessed by FACT-Br, toxicity, and neurocognitive function. The trial has been approved by the Institutional Review Board (IRB) and currently is enrolling patients. Clinical trial information: NCT05553522 .
A phase II, multicenter, prospective study of sacituzumab govitecan in recurrent glioblastoma.
Authors: Kelly William , Cordova Christine , Vaillant Brian D. , Balinda Henriette , Michalek Joel , Gilbert Andrea , Floyd John , Brenner Andrew J.
Published: July 2024

TPS2094

Background: Despite decades of research, glioblastoma (GBM) remains the most common and aggressive primary brain malignancy. GBM has been shown to express trophoblast cell-surface antigen 2 (Trop2) and this expression corelates with proliferation rate, micro vessel density, histological grade and clinical survival1,2. Antibody drug conjugates (ADC) targeting cell surface receptors have been recently shown to produce intracranial response rates of 25-44%%3-5. Sacituzumab Govitecan (SG) consists of an ADC targeting Trop2 attached via linker to a chemotherapy payload, SN-38. In 2020, it received FDA approved for the treatment of metastatic triple-negative breast cancer followed by HR+/HER2- metastatic breast cancer in 2023. Methods: This is a multi-center, open-label, prospective, single-arm phase 2 study using a 2-stage adaptive Bayesian design. Patients with GBM (IDH wild-type), recurrent following standard-of-care chemoradiation, received SG at 10mg/kg IV on days 1 and 8 of a 21 day cycle. Patients were assessed by RANO and CTCAE v5. The primary endpoint was progression-free survival of patients on SG as compared to a historical control of lomustine monotherapy. Enrollment was conducted at UT Health Science Center in San Antonio, Cleveland Clinic and Texas Oncology in Austin. A total of 23 patients have been screened with 3 screen failures and 20 patients enrolled. The study has now entered interim analysis. Trial Registration: This trial (NCT04559230) is enrolled at Clinical Trials.gov as “Sacituzumab Govitecan in Recurrent Glioblastoma”: https://clinicaltrials.gov/study/NCT04559230 Funding: WK and AB have received contracted funding from Gilead. Additional support provided by an NCI Cancer Center Support Grant (P30CA016672) and an Early Clinical Investigator Award through CPRIT (RP210164). References: 1. Ning, S., et al., TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas. Neurol Sci, 2013. 34(10): p. 1745-50; 2. Harvard, B.I.o.M.a., Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNA expression and clinical features; 3.Fabi, A., et al., T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer. Breast, 2018.41: p. 137-143; 4. Jacot, W., et al., Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res Treat, 2016. 157(2): p. 307-318. Clinical trial information: NCT04559230 .
A phase 1/2 dose escalation and expansion study of sonodynamic therapy with SONALA-001 in combination with Exablate 4000 Type 2.0 MR-guided focused ultrasound in patients with progressive or recurrent glioblastoma (rGBM).
Authors: Placantonakis Dimitris , Grabowski Matthew , Burns Terry C. , Butowski Nicholas A. , Fenn Peter , Clanton Ryan , Henry Lenora , Potter Wyatt , Andresen Corina , Marcus Stuart , Benaim Ely
Published: July 2024

TPS2101

Background: Recurrent glioblastoma (rGBM) is a lethal brain tumor with no effective therapy and an extremely poor prognosis (median survival 6 to 8 months after first recurrence). Sonodynamic therapy (SDT) is a non-invasive combination treatment that utilizes a drug, aminolevulinic acid HCL (SONALA-001), and a device, the Exablate 4000 Type 2.0, to deliver non-ablative MR-guided focused ultrasound (MRgFUS) to tumor. Preclinical studies have shown that SDT-induced sonoluminescence activates protoporphyrin IX (PpIX), which in turn generates reactive oxygen species that lead to tumor cell death and improved survival in animal glioma models. A first-in-human Phase 0 trial (NCT04559685) indicated that SONALA-001 SDT was well-tolerated and not associated with off-target cellular or radiographic effects, and provided direct evidence of reactive oxygen species formation and targeted tumor cell death in recurrent high-grade glioma (rHGG). Methods: SDT-202 is a Phase 1/2 multicenter, open-label, dose escalation and expansion study (NCT05370508) of 10 mg/kg iv SONALA-001 in combination with MRgFUS for SDT in patients with progressive or recurrent GBM. Treatments take place every 4 weeks. In phase 1, sonication energy escalation utilizes an accelerated titration design with a single subject for dose level 1, followed by cohorts 2 and 3 with 3+3 design for additional dose escalation. SONALA-001 is administered 6 to 12 hours prior to MRgFUS treatment. Once the RP2D is determined, Phase 2 dose expansion will enroll approximately 36 additional subjects to assess safety and efficacy of repeated cycles of SONALA-001 SDT at the optimized RP2D. Endpoints of this study are safety evaluation, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and determination of pharmacokinetic (PK) parameters. The Phase 2 portion will further characterize safety of RP2D along with evaluation of efficacy with PFS6 (mRANO), ORR, CBR, DOR, DOCR, TTR, and OS. Clinical trial information: NCT05370508 .
Evidence Against a Traumatic Brain Injury “July Effect”: An Analysis of 3 160 452 Patients From the National Inpatient Sample
Authors: Gajjar Avi A. , Covell Michael M. , Prem Kumar Rohit , Tang Oliver Y. , Ranganathan Sruthi , Muzyka Logan , Mualem William , Rehman Inaya , Patel Shrey V. , Lavadi Raj Swaroop , Mitha Rida , Lieber Bryan A. , Hamilton D. Kojo , Agarwal Nitin
Published: July 2024

BACKGROUND AND OBJECTIVES:

The “July Effect” hypothesizes increased morbidity and mortality after the addition of inexperienced physicians at the beginning of an academic year. However, the impact of newer members on neurosurgical teams managing patients with traumatic brain injury (TBI) has yet to be examined. This study conducted a nationwide analysis to evaluate the existence of the “July Effect” in the setting of patients with TBI.

METHODS:

The Healthcare Cost and Utilization Project Central Distributor's National Inpatient Sample data set was queried for patients with TBI using International Classification of Diseases (ICD)-9 and ICD-10 codes. Discharges were included for diagnoses of traumatic epidural, subdural, or subarachnoid hemorrhages. Only patients treated at teaching hospitals were included to ensure resident involvement in care. Patients were grouped into July admission and non-July admission cohorts. A subgroup of patients with neurotrauma undergoing any form of cranial surgery was created. Perioperative variables were recorded. Rates of different complications were assayed. Groups were compared using χ2 tests (qualitative variables) and t-tests or Mann-Whitney U-tests (quantitative variables). Logistic regression was used for binary variables. Gamma log-linked regression was used for continuous variables.

RESULTS:

The National Inpatient Sample database yielded a weighted average of 3 160 452 patients, of which 312 863 (9.9%) underwent surgical management. Patients admitted to the hospital in July had a 5% decreased likelihood of death (P = .027), and a 5.83% decreased likelihood of developing a complication (P < .001) compared with other months of the year. July admittance to a hospital showed no significant impact on mean length of stay (P = .392) or routine discharge (P = .147). Among patients with TBI who received surgical intervention, July admittance did not significantly affect the likelihood of death (P = .053), developing a complication (P = .477), routine discharge (P = .986), or mean length of stay (P = .385).

CONCLUSION:

The findings suggested that there is no “July Effect” on patients with TBI treated at teaching hospitals in the United States.
Gamma Knife Radiosurgery for Hypothalamic Hamartoma: A Multi-Institutional Retrospective Study on Safety, Efficacy, and Complication Profile
Authors: Tripathi Manjul , Sheehan Jason P. , Niranjan Ajay , Ren Lydia , Pikis Stylianos , Lunsford L. Dade , Peker Selcuk , Samanci Yavuz , Langlois Anne Marie , Mathieu David , Lee Cheng Chia , Yang Huai Che , Deng Hansen , Rai Ashutosh , Kumar Narendra , Sahu Jitendra Kuma , Sankhyan Naveen , Deora Harsh
Published: July 2024

BACKGROUND AND OBJECTIVES:

Gamma knife radiosurgery (GKRS) is a safe and effective treatment option for hypothalamic hamartomas (HH), but there is no consensus opinion on its timing, dosage, and follow-up. The aim of this study was to define the safety, efficacy, outcome, and complication profile of GKRS in this patient population.

METHODS:

This retrospective multicentric study involved 39 patients with the mean age of 16 ± 14.84 years. Early seizures resulted in an earlier age of diagnosis in 97% of patients. At baseline, no endocrine abnormalities were seen in 75% of patients while 18.9% showed precocious puberty (PP). The median target volume was 0.55 cc (0.1-10.00 cc), and a median margin dose of 16 Gy (8.1-20.0 Gy) was delivered in a single session. All patients were evaluated for clinical, endocrinological, and radiological outcomes.

RESULTS:

The median follow-up was 5 (0.1-15) years. The median target volume of the cohort was 0.55 (0.35-1.77) cc. The largest HH was of 10 cc. 24/39 (61.5%) were small HH (Regis I-III). At presentation, 94.8% patients suffered from seizures (87.18% with gelastic seizures). 7/39 patients (17.9%) were presented with both PP and epilepsy. Only one (2.6%) patient presented with PP alone. 29 patients had more than 3-year follow-up. All received ≥16 Gy targeting complete HH. 28% of patients showed regression in HH volume. Patients with Regis grade I-III and longer follow-up (>75 months) showed gradual improvement in seizures. 16/29 patients (55.2%) achieved good seizure control (Engel I/II) while 13 (44.8%) were in Engel III/IV status. Nine patients needed adjuvant treatment because of poor seizure control. Eight patients suffered from transient increase in seizures. One patient developed poikilothermia, and 2 patients developed new onset hormonal deficiency.

CONCLUSION:

GKRS is a safe and effective modality for treatment of HH with significant improvement in seizure control with minimal disruption of endocrine profile. It provides an excellent safety, efficacy, and complication profile, especially for small HH. Latency of results and its adjuvant nature remain the areas of research and breakthroughs among contemporary treatment options.
Mechanisms controlling haemolymph circulation under resting conditions in the Chagas disease vector Rhodnius prolixus
Authors: Villalobos Sambucaro María José , Alzugaray María Eugenia , Ronderos Jorge Rafael
Published: July 2024

Chagas disease vectors can ingest several times their own volume in blood with each meal. This ad libitum feeding causes an intense process of diuresis, inducing the insect to eliminate a large quantity of urine and faeces. To ensure diuresis, the speed of circulation of the haemolymph is increased. The Triatominae circulatory system is quite simple, including the dorsal vessel, which pumps haemolymph in an anterograde direction. The return is caused by peristaltic contractions of the anterior midgut. Triatominae insects can spend several weeks without feeding, meaning that most of the time, the insect is in a resting condition. Although the mechanisms controlling the circulation of the haemolymph during post-prandial diuresis have been largely analysed, the mechanisms controlling it during resting conditions are poorly understood. In this study, we analysed several canonical pathways (i.e. L-type VGCC, GPCR, RyR, IP3R) and a novel system represented by the recently characterized Piezo proteins. Our results show that during the resting condition, haemolymph circulation depends on a cross-talk between myogenic activity, inhibitory and stimulatory cellular messengers, and Piezo proteins. This report also unveils for the first time the existence of a putative Piezo protein in Hemiptera.
Effect of Supplemental Oxygen on Physiological Responses to Exercise in Fibrotic Interstitial Lung Disease
Authors: BAIDATS YAEL , KADOSH SHIR , JONES ANDREW M. , WILKERSON DARYL , VELNER ARIELA , REUVENY RONEN , SEGEL MICHAEL J.
Published: July 2024

Purpose

We studied the effect of O2 supplementation on physiological response to exercise in patients with moderate to severe interstitial lung disease (ILD).

Methods

Thirteen patients (age 66 ± 10 yr, 7 males) with ILD (total lung capacity, 71% ± 22% predicted; carbon monoxide diffusion capacity, 44% ± 16% predicted) and 13 healthy individuals (age 50 ± 17 yr, 7 males) were tested. ILD patients performed symptom-limited cardiopulmonary exercise tests and constant work rate (WR) tests at 80% of the WR at the gas exchange threshold. Tests breathing room air (RA; 21% O2) were compared with tests performed breathing 30% O2. Oxygen uptake (V̇O2) kinetics were calculated from the constant WR test results.

Results

In the ILD group, peak WR, peak V̇O2, and V̇O2 at the gas exchange threshold improved significantly when breathing 30% O2 compared with RA (mean ± SD, 75 ± 26 vs 66 ± 23 W, 17 ± 4 vs 15 ± 2 mL·kg−1·min−1, and 932 ± 245 vs 854 ± 232 mL·min−1; P = 0.004, P = 0.001, and P = 0.01, respectively). O2 saturation (SpO2%) at peak exercise was higher with 30% O2 (97% ± 4% vs 88% ± 9%, P = 0.002). The time constant (tau) of V̇O2 kinetics was faster in ILD patients while breathing 30% O2 (41 ± 10 s) compared with RA (52 ± 14 s, P = 0.003). There was a negative linear relation between tau and SpO2% with RA (r = −0.76, P = 0.006) and while breathing 30% O2 (r = −0.68, P = 0.02).

Conclusions

Using a clinically applicable level of O2 supplementation (30%) improved maximal, aerobic exercise capacity and V̇O2 kinetics in ILD patients, likely due to increased blood O2 content subsequently increasing the O2 delivery to the working muscles.
The Physiological and Performance Development of Two Multiple Olympic Champion Rowers: A 20-Year Follow-Up Study
Authors: MIKULIC PAVLE , GULIN JERE
Published: July 2024

Purpose

This study reports the results of a 20-yr (2005 to 2024) follow-up study of two 2-time Olympic and 6-time world champion rowing athletes. To provide a comprehensive picture of adaptations in physiological and performance characteristics to long-term training, we monitored the athletes’ physiological and performance data annually through five 4-yr developmental phases.

Methods

Maximal oxygen uptake (V̇O2max), maximal minute power (MMP), and power output corresponding to anaerobic threshold (PAT) were derived from a rampwise exercise test on a rowing ergometer. In addition, average power output sustained during all-out tests over 2000 and 6000 m on a rowing ergometer was also obtained.

Results

V̇O2max peaked at age 22 for athlete A and at age 25 for athlete B (at ~7 L·min−1) before stabilizing and then gradually declining to a range of 6.2 to 6.5 L·min−1 for both athletes. MMP stabilized in both rowers at values between 550 and 575 W and displayed minimal fluctuations over the final two phases of the study. In addition, MMP closely resembled the corresponding average power output sustained during the 2000-m all-out tests on a rowing ergometer. Average power output during 2000 and 6000-m all-out tests showed steady improvements over the monitored phases of the study, with the highest power output crew averages for both 2000-m (532 W; 5 min 48 s) and 6000-m (463 W; 18 min 4 s) tests recorded during the last 4-yr phase of the assessment.

Conclusions

Improvements in rowing ergometer performance over 2000 and 6000 m appear to be largely independent of the multiyear changes in V̇O2max. Long-term rowing training resulted in continuous improvements in MMP and PAT throughout the monitored phases, which more closely mimicked improvements in rowing ergometer performance.
Ο ρόλος των μεσεγχυματικών κυττάρων εκ λιπώδους ιστού στην επούλωση αναστομώσεων παχέος εντέρου σε φλεγμονώδη νόσο του εντέρου
Authors: Νταμπάκης Γεώργιος
Published: July 2024

Ο σκοπός της πειραματικής μελέτης είναι η χρήση μεσεγχυματικών κυττάρων εκ λιπώδους ιστού σε αναστόμωση εντέρου σε περιβάλλον φλεγμονής, για τη διερεύνηση των αντιφλεγμονωδών ιδιοτήτων των κυττάρων αυτών. Συνολικά 24 επίμυες της κατηγορίας Wistar χωρίστηκαν σε 4 ομάδες από 6 πειραματόζωα και υποβλήθηκαν σε χειρουργική επέμβαση διατομή του παχέος εντέρου και τελικο-τελική αναστόμωση. Στις δύο ομάδες χορηγήθηκε DSS 5% για την πρόκληση οξείας φλεγμονής, ενώ οι υπόλοιπες ομάδες παρέμειναν χωρίς φλεγμονή . Στις δύο ομάδες με την φλεγμονή ενέθηκαν 5x10^6 μεσεγχυματικών κυττάρων στην αναστόμωση ή 70μl PBS αντίστοιχα. Σε μία ομάδα πραγματοποιήθηκε μόνο χειρουργική επέμβαση, και σε μία ομάδα έγινε χειρουργική επέμβαση και ενέθηκαν 5x10^6 μεσεγχυματικών κυττάρων. Την 8η μετεγχειρητική ημέρα οι επίμυες θυσιάστηκαν και δείγμα εντέρου που περιέχει την αναστόμωση απομονώθηκε. Οι μεταβλητές που μετρήθηκαν είναι το: μακροσκοπικό σκορ επιπλοκών, πίεση διάσπασης αναστόμωσης, TNF-a, IL6, VEGF, Ιστολογικό σκορ – ιστολογική αξιολόγηση της φλεγμονής και Υδροξυπρολίνη. Σημαντικά χαμηλότερα ποσοστά μετεγχειρητικών επιπλοκών και υψηλότερη πίεση διάσπασης αναστόμωσης παρατηρήθηκαν στις ομάδες που έλαβαν μεσεγχυματικά κύτταρα. Οι προ-φλεγμονώδεις κυτοκίνες IL6 και TNFa ήταν σημαντικά χαμηλότερες ενώ η VEGF παρότι οριακά αυξημένη, δεν έφτασε σε στατιστικά σημαντικές διαφορές ανάμεσα στις ομάδες. Επίσης παρατηρήθηκε εντονότερη έκφραση M2 φαινότυπος στα μακροφάγα των ομάδων που έλαβαν μεσεγχυματικά κύτταρα και το ιστολογικό σκορ δεν έδειξε στατιστικά σημαντική διαφορά μεταξύ των δύο ομάδων με την φλεγμονή. Συμπερασματικά, έγχυση των μεσεγχυματικών κυττάρων εκ λιπώδους ιστού την 8η μετεγχειρητική ημέρα, βελτιώνουν την ποιότητα της αναστόμωσης σε περιβάλλον φλεγμονής, έχοντας τοπική αντιφλεγμονώδη δράση. Παρόλα αυτά στην ίδια χρονική στιγμή δεν φαίνεται να υπάρχουν σημαντικές διαφορές όσον αφορά στην νεοαγγειογένεση καθώς και στα ιστολογικά χαρακτηριστικά των αναστομώσεων.
Design and Implementation of Fabric Wrinkle Detection System Based on YOLOv5 Algorithm
Authors: Li Cheng , Fu Tianyu , Li Fengming , Song Rui
Published: July 2024

Background Nowadays, robots have been widely used in handling rigid objects, but research on deformable objects like fabrics is still in its early stages. This is because fabrics possess infinite degrees of freedom and their state modeling is highly complex, making robot manipulation of fabrics challenging due to the occurrence of wrinkles and deformations during the operation. The detection and recognition of fabric deformations such as wrinkles and fabric manipulation features like corners are of great significance in enhancing a robot's capability to handle deformable objects. Methods In response to the issue of fabric wrinkles in various scenarios, we propose a real-time fabric wrinkle and corner detection system based on the YOLOv5 detection algorithm. Additionally, we implement a fabric flattening operation on a hardware platform using the detected wrinkle and corner information. Results We collected and created a dataset of fabric deformation features and trained a detection model, achieving a detection accuracy of over 90%. The model was deployed in the fabric wrinkle detection system, using a heuristic operation strategy of flattening the fabric from the four corners. As a result, the robot successfully performed the flattening operation on wrinkled fabric. Conclusions The application of the YOLOv5 algorithm enables effective detection of fabric wrinkles and corner points. Based on the detection information and using the quadrilateral flattening operation method, the robotic system achieves fabric flattening operations.
The effects of mouth rinsing and gargling with mouthwash containing povidone-iodine and hydrogen peroxide on the cycle threshold value of Severe Acute Respiratory Syndrome Coronavirus 2: A randomized controlled trial of asymptomatic and mildly symptomatic patients
Authors: Sulistyani Lilies Dwi , Julia Vera , Soeprapto Andrianto , Swari Rumartha Putri , Rosmanato Febriadi , Haryanto Budi , Cahyarini Cahyarini , Panjaitan Rinaldi , Maharani Diah Ayu
Published: July 2024

Background Coronavirus disease 2019 can spread rapidly. Surgery in the oral cavity poses a high risk of transmission of severe acute respiratory syndrome coronavirus 2. The American Dental Association and the Centers for Disease Control and Prevention recommend the use of mouthwash containing 1.5% hydrogen peroxide (H2O2) or 0.2% povidone iodine (PI) to reduce the viral load in the upper respiratory tract and decrease the risk of transmission. The aim of the present study was to analyze the effect of mouth rinsing and gargling with mouthwash containing 1% PI, 0.5% PI, 3% H2O2, or 1.5% H2O2 and water on the cycle threshold (CT) value obtained by real-time reverse transcription polymerase chain reaction (RT-PCR). Methods This study is a randomized single blind controlled clinical trial which has been registered in the International Standard Randomized Controlled Trial Number (ISRCTN) registry on the 3rd February 2022 (Registration number: ISRCTN18356379). In total, 69 subjects recruited from Persahabatan General Hospital who met the inclusion criteria were randomly assigned to one of four treatment groups or the control group. The subjects were instructed to gargle with 15 mL of mouthwash for 30 s in the oral cavity followed by 30 s in the back of the throat, three times per day for 5 days. CT values were collected on postprocedural days 1, 3, and 5. Results The results of the Friedman test significantly differed among the groups (n=15). The CT values increased from baseline (day 0) to postprocedural days 1, 3, and 5. Conclusions Mouth rinsing and gargling with mouthwash containing 1% PI, 0.5% PI, 3% H2O2, or 1.5% H2O2 and water increased the CT value.
Analysis on short-term outcomes of patients with thoracic trauma at dr. Zainoel Abidin General Hospital in Banda Aceh
Authors: Habibie Yopie Afriandi , Anisa Widya , Nurkhalis Nurkhalis , Azharuddin Azharuddin , Ridwan Muhammad
Published: July 2024

Background Thoracic trauma is defined as a trauma that hits the chest wall directly or indirectly, either as a result of blunt or penetrating trauma. Thoracic trauma can occur in any age or genders, and become a life-threatening if the treatment isn’t immediate and appropriate. Methods This research was an observational study with a cohort retrospective design using secondary data in the form of thoracic trauma patients at The Zainoel Abidin General Hospital, Banda Aceh, Indonesia in the period January 2019-December 2020. The statistical analysis used were chi square for bivariate and multivariate analysis, spesifically logistic regression analysis was conducted to know which risk factor influences the most. Result There were 141 medical records used in this study, thoracic trauma was more common in men compared to women. The age group of 46-55 is the age group with the highest percentage of thoracic trauma patients, road traffic are the leading cause of thoracic trauma where the most common diagnosis is rib fractures. Significant factors that associated with the short outcome of thoracic trauma are thoracic trauma diagnosis (p=0,00), management of thoracic trauma (p=0,00), ventilator (p=0,04), duration of ventilator (p=0.01), sepsis (p=0,00), qSOFA score (p=0,00) and injury severity score (p=0,00). Conclusions Vehicle accidents contributed to a considerable number of traumatic chest injuries in this study. Diagnosis, management of trauma, days of ventilation, qSOFA score, injury severity score, and development of sepsis were associated with the short-term outcome among thoracic trauma patients. Injury severity score seems to be the most influential variable in this study, the lower the better it is. Road safety intervention is urgently needed to control the underlying problems in this study.
Case Report: Wellens syndrome in acute critical coronary occlusion saved by collateral
Authors: Alsagaff Mochamad Yusuf , Putra Tony Santoso , Khrisna Bagus Putra Dharma , Nugraha Ricardo Adrian
Published: July 2024

Background It is important and challenging to distinguish between acute myocardial infarction and Wellens syndrome due to its time to intervention. Difficulties in differentiating between subtypes could mean the patients are overtreated or receive undertreatment. Case report A 57-year-old man was referred to our emergency ward with acute onset of chest pain. Electrocardiograms changes were suggestive of type A Wellens syndrome. Nitroglycerin was administrated, the patient's chest pain disappeared, and we planned an early invasive strategy. He had a previous documented electrocardiogram before he went for catheterization and based on the second electrocardiogram changes were suggestive of an ST-elevation. As the result of the invasive strategy, it was found that there was single-vessel disease, critical occlusion in the middle of the left anterior descending artery coronary artery with collateral from the right coronary artery. After two days of observation in the Intensive Cardiovascular Care Unit, the patient improved and was transferred to Low Care Unit. Conclusions The case highlights Wellens syndrome in acute critical occlusion with collateral artery.