bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic survey sequencing and complete mitochondrial genome of the elkhorn coral crab Domecia acanthophora (Desbonne in Desbonne & Schramm, 1867) (Decapoda: Brachyura: Domeciidae)
Authors: Bravo Henrique , Baeza J Antonio , van der Meij Sancia E T 
Published: August 2023

Abstract
The elkhorn coral crab Domecia acanthophora inhabits shallow-water coral reefs in the Western Atlantic. The species has a wide distribution and, although primarily associated with endangered Acropora corals, has been recorded from a myriad of hosts. Here we conducted the first genomic survey and complete mitochondrial assemblage and characterisation of any species of Domeciidae, as well as the first species within Trapezioidea. The estimated size of the nuclear genome ranged from 0.64 Gbp to 1.76 Gbp, revealing a small genome. Repetitive elements of the genome were estimated here at 66.4% and 74%, respectively, with the majority of the repetitive elements consisting of LINE, LTR, and satellite DNA. The assembled A-T rich mitochondrial genome consisted of 15,568 bp in length, with 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes and two ribosomal RNA (rRNA) genes. A 619 bp long non-coding region was identified as the supposed D-loop/control region, containing eight microsatellites. The 22 tRNA genes, ranging from 65 to 71 bp in length, displayed a typical “cloverleaf” secondary structure, with the exception of tRNA-Ser1 which lacked part of the DHU arm and tRNA-Asp displayed a deletion of the TΨC loop but not the arm. Two transposition events of two tRNA genes were also found when comparing the gene order of D. acanthophora to that of the brachyuran basic gene order, which had not been reported before. Despite belonging to a widely distributed, well-known superfamily of coral-associated crabs, the Trapezioidea, very little was known about this species from a genetics perspective, which is remedied here by providing a new genomic resource for D. acanthophora.
Statistical characteristics of observed and simulated dark matter haloes
Authors: Demiański M , Doroshkevich A , Larchenkova T , Pilipenko S 
Published: August 2023

ABSTRACT
A simple model of spherical dark matter haloes is proposed in terms of two structure functions. In the framework of this model, we analysed the properties of 450 000 simulated haloes with masses Mvir &gt; 1011 M⊙. We compared the mean characteristics of simulated haloes with the corresponding characteristics of 641 galaxies and found that the basic characteristics of the two populations are similar but that their probability distribution functions are different. This disagreement may be caused by technical factors such as the halo identification algorithm, which does not reproduce the observed dark matter haloes correctly.
The identification of a novel orally available ferroptosis inducer for the treatment of clear cell renal carcinoma
Authors: Koh Mei Yee 
Published: August 2023

Abstract

Background
Background: Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is typically initiated by inactivation of the von Hippel Lindau (VHL) gene resulting in constitutive activation of the hypoxia inducible factors, HIF-1α and HIF-2α. HIF-2α is a central driver of kidney cancer progression and is a well validated therapeutic target for ccRCC. Additionally, VHL loss and HIF activation promote lipid accumulation that increases the sensitivity of ccRCC cells to ferroptosis, a form of cell death characterized by iron dependent lipid peroxidation. However, classical inducers of ferroptosis, which induce ferroptosis in vitro, show limited activity in vivo due to possible redundancies in the extracellular space, suggesting a need for novel molecular targets for the induction of ferroptosis in vivo for therapeutic benefit.

Methods
Method: We performed a high-throughput screen to identify small molecule inhibitors of HIF-2α and performed additional validation and structure activity relationship studies to identify compounds with improved potency of HIF-2α inhibition. The molecular target of these inhibitors was determined by mass spectrometry using the Drug Affinity Responsive Target Stability (DARTS) assay, and target validation was confirmed using siRNA knockdown and NMR. In vivo anti-tumor efficacy was verified using syngeneic RENCA cells injected into Balb/C mice. Exposure to KD061 was verified using LC-MS/MS detection of KD061 in the plasma and tumors of treated mice.

Results
Results: We identified a novel molecule, KD061, which decreases levels of HIF-1/2α and induces ferroptosis in vivo through oral administration by targeting Iron Sulfur Cluster Assembly 2 (ISCA2). ISCA2 is a component of the late mitochondrial Iron Sulfur Cluster (L-ISC) assembly complex and ISCA2 inhibition either pharmacologically or using siRNA triggers the iron starvation response, resulting in iron/metals overload and death via ferroptosis. Cell death induced by KD061 was decreased by re-expression of VHL, suggesting synthetic lethality in the context of VHL loss. ISCA2 inhibition also decreased HIF-2α protein levels by blocking iron-responsive element (IRE)-dependent translation, and at higher concentrations, also decreased HIF-1α translation through unknown mechanisms. Treatment of tumor-bearing RENCA-Balb/C mice with KD061 significantly reduced tumor growth in vivo, decreased HIF-α levels and increased lipid peroxidation, suggesting increased ferroptosis in vivo. Treatment with KD061 was well tolerated at the therapeutic dose with no detectable effects on blood chemistry and blood counts.

Conclusions
Conclusions: Here, we describe the first orally available inducer of ferroptosis with anti-tumor efficacy in vivo. The targeting of ISCA2 using KD061 is a promising therapeutic strategy to inhibit HIF-1/2α and to induce ferroptosis in pVHL deficient cells.
CDMRP DOD Funding: yes
NRG-GU012: randomized phase II stereotactic ablative radiation therapy (SABR) for metastatic unresected renal cell carcinoma (RCC) receiving immunotherapy (SAMURAI)
Authors: McKay Rana 
Published: August 2023

Abstract

Background
Background: It is estimated that a significant number of patients presenting with metastatic RCC are either ineligible, not recommended for, or refuse surgery. There remains no well-established method for addressing the primary tumor in such patients. Stereotactic ablative radiotherapy (SABR) is a highly effective modality for the treatment of the primary tumor in RCC. Our study seeks to evaluate SABR as an alternative approach to treat the primary tumor in patients with metastatic RCC receiving immunotherapy, who are not recommended for surgery, or who decline surgery. The primary objective of the study is to determine whether the addition of SABR to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC). The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria. Patients are eligible if they are not recommended for upfront surgery, have a primary tumor treatable with SABR, and are candidates for immunotherapy. Immunotherapy is physician’s choice and will include either two different immunotherapy regimens (IO-IO) or immunotherapy in combination with a VEGF inhibitor (IO-VEGF).

Methods
240 patients will be randomized in a 2:1 ratio favoring SABR plus immunotherapy (n=160) as compared to standard of care immunotherapy alone (n=80). The sample size will provide 90% power at a one-sided alpha level of 0.05 to detect a hazard ratio for nrPFS of 0.61, i.e., a 40% reduction in the rate of events. One-year PFS in the nivolumab plus ipilmumab arm was 50% (n=550, intermediate/poor risk population). Checkmate 9ER (Choueiri 2021) showed a one-year PFS rate in patients receiving nivolumab plus Cabozantinib (n=323) of 45-58% (intermediate/poor risk population). We have therefore estimated a one-year nrPFS rate of 50% in the control (immunotherapy alone) arm for SAMURAI. We expect nephrectomies to contribute only a small fraction to the total nrPRS events. To detect a hazard ratio of 0.62, which corresponds under exponential distribution assumptions to an absolute 15% improvement in one-year nrPFS from 50% in the control group to 65% in the experimental arm (SABR plus immunotherapy), a total sample size of 240 patients will be enrolled. This design will provide 90% power, based on a one-sided logrank test at the 0.05 alpha level, with three years of accrual and two further years of follow-up. The expected number of nrPFS events is E=175. The calculations allow for a 10% non-eligible/early dropout rate. The trial is currently open and accruing through the NRG oncology cooperative group (NCT05327686).
Pathogen-induced m6A dynamics affect plant immunity
Authors: Prall Wil , Sheikh Arsheed H , Bazin Jeremie , Bigeard Jean , Almeida-Trapp Marilia , Crespi Martin , Hirt Heribert , Gregory Brian D 
Published: August 2023

AbstractPosttranscriptional regulation of mRNA mediated by methylation at the N6 position of adenine (N6-methyladenosine [m6A]) has profound effects on transcriptome regulation in plants. Focused studies across eukaryotes offer glimpses into the processes governed by m6A throughout developmental and disease states. However, we lack an understanding of the dynamics and the regulatory potential of m6A during biotic stress in plants. Here, we provide a comprehensive look into the effects of m6A on both the short-term and long-term responses to pathogen signaling in Arabidopsis (Arabidopsis thaliana). We demonstrate that m6A-deficient plants are more resistant to bacterial and fungal pathogen infections and have altered immune responses. Furthermore, m6A deposition is specifically coordinated on transcripts involved in defense and immunity prior to and proceeding the pathogen signal flagellin. Consequently, the dynamic modulation of m6A on specific stress-responsive transcripts is correlated with changes in abundance and cleavage of these transcripts. Overall, we show that the m6A methylome is regulated prior to and during simulated and active pathogen stress and functions in the coordination and balancing of normal growth and pathogen responses.
Walking Exercise Sustainability Through Telehealth for Veterans With Lower-Limb Amputation: A Study Protocol
Authors: Hanlon Shawn L , Swink Laura A , Akay Rachael Brink , Fields Thomas T , Cook Paul F , Gaffney Brecca M M , Juarez-Colunga Elizabeth , Christiansen Cory L 
Published: August 2023

Abstract

Objective
This randomized controlled superiority trial will determine if an 18-month telehealth walking exercise self-management program produces clinically meaningful changes in walking exercise sustainability compared to attention-control education for veterans living with lower-limb amputation.

Methods
Seventy-eight participants with lower-limb amputation (traumatic or nontraumatic) aged 50 to 89 years will be enrolled. Two groups will complete 6 one-on-one intervention sessions, and 6 group sessions over an 18-month intervention period. The experimental arm will receive a self-management program focusing on increasing walking exercise and the control group will receive attention-control education specific to healthy aging. Daily walking step count (primary outcome) will be continuously monitored using an accelerometer over the 18-month study period. Secondary outcomes are designed to assess potential translation of the walking exercise intervention into conventional amputation care across the Veteran Affairs Amputation System of Care. These secondary outcomes include measures of intervention reach, efficacy, likelihood of clinical adoption, potential for clinical implementation, and ability of participants to maintain long-term exercise behavior.

Impact
The unique rehabilitation paradigm used in this study addresses the problem of chronic sedentary lifestyles following lower-limb amputation through a telehealth home-based walking exercise self-management model. The approach includes 18 months of exercise support from clinicians and peers. Trial results will provide rehabilitation knowledge necessary for implementing clinical translation of self-management interventions to sustain walking exercise for veterans living with lower-limb amputation, resulting in a healthier lifestyle.
COVID-19 surge testing in a unitary local authority in England: an observational study
Authors: Norman Grace , Akomfrah George , Mytton Oliver , Brown Ian 
Published: August 2023

Abstract

Background
In May 2021, due to rising case rates and the detection of a new variant of concern, increased asymptomatic ‘surge testing’ for COVID-19 was implemented in Bedford Borough.

Methods
Over 3 weeks, surge testing in higher incidence areas utilized: (i) mobile testing units, (ii) home test kit collection and drop-off and (iii) Door-to-door outreach. Testing was voluntary and supported by a communication campaign. Test results and data provided by participants were analyzed.

Results
During surge testing, 16% (n = 5018) of the target population were tested, resulting in 125 positive results (2.5%). Females, those identifying as white, and those living in the most deprived quintile (Q1) were over-represented in testing. Test positivity was relatively higher for ages 0–19 (4.0%), for minority ethnic groups (2.8%), and those not listing an ethnic group (15.1%). Test positivity was lowest for the door-to-door outreach approach (0.9%), despite collecting the most samples (2225).

Conclusions
Surge testing in Bedford reached a large number of people, was particularly successful at reaching people living in the most deprived areas, and identified cases that might have otherwise been missed. However, the testing did not reach the majority of the population, and began after new infections had begun to fall.
Effect of Intra Operative Intravenous Lidocaine Infusion on Control of Pain and Recovery of Intestinal Function Following Surgical Appendectomy
Authors: Ibrahim Ahmed Saeed Mohamed , El-Shazly Ghanim Ahmad , Abdelaal Wail Ahmed Mohamed 
Published: August 2023

Abstract

Background
Intravenous lidocaine infusion has been shown to facilitate postoperative recovery after major abdominal surgery. This current randomized controlled study will assess the effect of intraoperative intravenous lidocaine infusion on pain intensity, bowel function and cytokine response after surgical appendectomy.

Aim of the Work
To determine the role of intraoperative lidocaine infusion in reducing perioperative pain and analgesia requirement and enhancing the recovery of intestinal function in patients undergoing surgical Appendectomy.

Patients and Methods
The current prospective randomized double-blinded study was conducted at the surgery department, Faculty of Medicine, Ain Shams University and it included 40 patients who were undergone urgent open appendectomy and met the selection criteria. They were classified into 2 groups: Group L: patient who received IV bolus injection of lidocaine (1.5 mg/kg slowly over 10 min) 30 minutes before the skin incisions followed by a continuous IV infusion at the rate of 2 mg/kg/h via infusion pump(B-BRAUN), Group S (control): patient who received 0.9% normal saline in equal volume and in the same manner.

Results
There was statistically significant difference between the studied groups regarding time to pass flatus. Patients within lidocaine group pass flatus significantly earlier than those with control group. There is statistically non-significant difference between the studied groups regarding postoperative complications.

Conclusion
From the current study, it was concluded that perioperative IV lidocaine injection had significant effect in reduction of postoperative pain and increased the main pain free period also noticed IV lidocaine decreased opioid requirement and time to pass flatus so shorten hospital stay. Perioperative IV lidocaine had no effect on postoperative complications and IV lidocaine during incision and extubation attenuated hemodynamic response.
Comparison of Propofol versus Midazolam Infusion for Conscious Sedation during Spinal Anaesthesia in Patients Undergoing Inguinal Hernia Repair
Authors: El Kady Galal Adel Abd El-Rahim , El-Sersi Mayar Hassan , Kassem Amr Ahmed , Hussein Ahmed Yasser Mohammed 
Published: August 2023

Abstract

Background
The operating room is an anxiety provoking environment. Supplemental sedation with an intravenous agent is often required to allay fear and anxiety in patients subjected to spinal anaesthesia. Sedation is a valuable tool to make surgery under regional anaesthesia convenient for the patient, the anaesthetist and the surgeon. Conscious sedation is a minimally depressed level of consciousness that retains the patient’s ability to maintain his or her airway independently and continuously and to respond appropriately to physical stimulation and verbal commands, produced by pharmacologic or non-pharmacologic methods alone or in combination.

Aim of the Work
This study will be designed to compare Propofol and Midazolam with regard to their suitability as sedative agents during spinal anaesthesia in terms of onset & recovery from sedation, haemodynamic stability, dosage and side effects of both the drugs.

Patients and Methods
This Interventional clinical study (Randomized double blinded study was conducted in Ain Shams University Hospital’s operating rooms through 3 months on 50 patients. After obtaining approval from the medical ethical committee in Ain Shams University Hospital’s operating rooms, a written informed consent was obtained from every patient after explaining the procedure.

Results
Based on this study the following conclusions have been made: Cardiovascular parameters and respiration were well maintained in both the study groups, no incidence of apnea was noticed in both the study groups, pain during the injection of propofol was a side effect noticed, onset of action was faster in the propofol group, propofol group was less co-operative than midazolam group but this was clinically insignificant, midazolam group showed slower recovery than propofol group restricting and wasting the productive time of the patient, qualities such as short plasma half-life period, absence of postoperative nausea and vomiting, make propofol a better choice for sedation and thus propofol is a fast acting, safe and easily controllable sedative with rapid recovery. This offered the advantage of early patient discharge and better patient compliance.

Conclusion
When given as a sedative adjunct to spinal I, both propofol and midazolam in equisedative infusions offer good anxiolysis and good cardio respiratory stability. Propofol has the advantage of providing faster onset of sedation, a rapid clear headed recovery from the same and lesser postoperative impairment of recall while midazolam offers better intraoperative amnesia.
Glycemic Control in Postoperative Patients in ICU (Comparative Study between Euglycemic Control and Mild Hyperglycemic Control in Patients Outcome)
Authors: Mustafa Zakaria Abdelaziz , El shebiny Ahmed Ali , koraitem Ahmed farouk , Abouzeid Fawzy kamel Abdelaziz 
Published: August 2023

Abstract

Background
Hyperglycemia is common complication in postoperative patients admitted to intensive care units, whether a patient has a history of diabetes or not. Hyperglycemia has been associated with increased perioperative morbidity and mortality.

Objective
To compare between outcome of euglycemia and mild hyperglycemia in postoperative patients admitted to ICU. And achieving the optimal target range for blood glucose in postoperative patients.

Patients and Methods
We conducted our prospective study on 70 postoperative patients admitted to ICU with blood glucose above 180 mg/dl we managed all of them with intravenous insulin with 2 different blood glucose level targets. Group one with euglycemic control aimed blood glucose level between 110 gm/dl to 140 gm/dl. Group two with mild hyperglycemia aimed blood glucose level target between 140 gm/dl to 180 gm/dl.

Results
We found in our study that euglycemic control didn’t significantly reduce the postoperative complications and improve the patients outcome in comparison to the mild hyperglycemic group. We also found that there is a mild lower rates of complications in non diabetic patients on euglycemic control compared with those non diabetics treated with mild hypoglycemic targets.

Conclusion
In our prospective study to compare between effects of euglymic control versus mild hyperglycemia we found that there is no significant difference in patients outcomes between patients controlled at target range 110 gm/dl to 140 gm/dl in comparison to the controlled group between blood glucose range 140 gm/dl to 180 gm/dl in postoperative patients admitted to ICU However there is less complications rates in non diabetics with euglycemic control group in comparison to non diabetics in group two (mild hyperglycemia). The optimal target for blood glucose level is a wide range from 110 mg/dl up to 180 mg/dl.
Acute Kidney Injury in Polytrauma Patients in Intensive Care Unit: A Prospective Observational Study
Authors: Elsaaedy Mohammed Ismael Abd Elfattah , El Gendy Hanaa Mohamed Abdullah , Abd El Hameed Gam al Eldin Adel , Ebrahim Mahmoud Abdelrahman Seifelnasr 
Published: August 2023

Abstract

Background
Acute Kidney Injury (AKI) is a common complication of severe trauma patients and is associated with increased morbidity and mortality. Injury Severity Score (ISS) &gt; 15 represents approximately 10% of all trauma patients in intensive care unit (ICU). The primary outcome of the study was to correlate between the AKI by using RIFLE criteria and the trauma severity by using ISS. While; the secondary outcomes were; identifying the incidence of AKI in polytrauma patients, the length of ICU and hospital stay and 28 days mortality.

Methods
This is a prospective observational study which was conducted during the period from May 2020 to September 2020. It Included 60 cases of polytrauma patients who have ISS&gt;15, at Ain shams university hospitals, their ages ranged from 18-70 years. All patients’ data were recorded for: Injury Severity Score (ISS). RIFLE criteria. Length of ICU and hospital stay. 28 days mortality.

Results
There was no correlation between the incidence of AKI and the severity of the trauma by using ISS. Incidence of AKI the percentage was (45 %) among all the studied cases. According to RIFLE criteria, within this population, patients were classified as (21.7%) of the patients in the Risk stage; (18.3%) of the patients in Injury stage, and (5%) of the patients in Failure stage. There was statistically significant difference between AKI and No AKI regarding risk factors, percentages of sepsis, rhabdomyolysis, drugs, abdominal trauma and hypovolemic shock were higher in AKI patients than No AKI patients. There was no statistically significant difference between AKI patients and No AKI patients regarding mechanical ventilation, ICU stay, Hospital stay and 28 d Mortality.

Conclusion
The incidence of acute kidney injury in polytrauma patients in the intensive care unit was high and the overall mortality of our patients was as high as that reported in other studies. A better comprehension of risk factors associated with trauma-associated AKI is important, such as rhabdomyolysis, sepsis, abdominal trauma (compartment) and hypovolemic shock.