Rat copper transport protein 2 (CTR2) is involved in fertilization through interaction with IZUMO1 and JUNO.

In mammalian reproduction, testis-specific protein IZUMO1 and its receptor JUNO on the oocyte surface are essential for sperm-oocyte recognition, binding, and membrane fusion. However, these factors alone are insufficient to accomplish cytoplasmic membrane fusion. It is believed that other gametic proteins interact with them to facilitate sperm-oocyte interaction on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. In this study, Copper Transport Protein 2 (CTR2) has been identified on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. CTR2 directly interacts with both IZUMO1 and JUNO, colocalizing with IZUMO1 on the sperm head and with JUNO on the oocyte membrane. Treatment of the capacitated sperm and zona pellucida-free oocytes with anti-CTR2 antibody resulted in a significant decrease in fertilization rates in IVF experiments. These findings suggest that CTR2 plays an important role in mammalian fertilization by interacting with IZUMO1 and JUNO, providing new insights into the molecular mechanisms of mammalian sperm-oocyte adhesion and fusion.

Inhibition of CTR1 expression improves hypoxia/reoxygenation-induced myoblast injury by blocking cuproptosis.

Skeletal muscle ischemia-reperfusion injury (IRI) is a common severe disease with a complex pathological process. This study found that copper chloride (CuCl2) inhibited cell viability in a concentration dependent manner, increased intracellular copper levels and downregulated copper transporter 1 (CTR1) expression. CTR1 upregulation promoted copper uptake by myoblasts and then enhanced cuproptosis, leading to a significant increase in the levels of dihydrolipoamide S-acetyltransferase (DLAT) oligomers, while a significant decrease in the levels of lipoylated (Lip)-dihydrolipoamide S-succinyltransferase (DLST) and Lip-DLAT, ultimately inhibiting cell viability and inducing cell injury. Inducing cuproptosis with elesclomol plus CuCl2 (ES + Cu) further confirmed that "ES + Cu" treatment significantly reduced the contents of adenosine triphosphate (ATP) and glutathione (GSH), decreased the activities of mitochondrial complex I and III, and increased the contents of lactate (LA), malondialdehyde (MDA), creatine kinase (CK) and lactate dehydrogenase (LDH); when tetrathiomolybdate (TTM) was added to inhibit cuproptosis, myoblast injury was recovered significantly. Meanwhile, hypoxia/reoxygenation (H/R) induced CTR1 expression, increased the levels of intracellular copper, DLAT oligomers, LA, MDA, CK and LDH, reduced the levels of Lip-DLST, Lip-DLAT, ATP and GSH, and weakened the activities of mitochondrial complex I and III; after knocking down CTR1 expression, the levels of intracellular copper and the activation of cuproptosis pathway were decreased, and cell viability, injury and inflammation levels were significantly improved. Therefore, cuproptosis can promote myoblast injury, while H/R enhances copper uptake by inducing CTR1 expression, thereby enhancing cuproptosis and inducing cell injury, indicating that cuproptosis is a new mechanism of H/R-induced myoblast injury.

Characterization of a High-Affinity Copper Transporter CTR1a in the White-Nose Syndrome Causing Fungal Pathogen Pseudogymnoascus destructans.

Copper is an essential micronutrient and the ability to scavenge tightly bound or trace levels of copper ions at the host-pathogen interface is vital for fungal proliferation in animal hosts. Recent studies suggest that trace metal ion acquisition is critical for the establishment and propagation of Pseudogymnoascus destructans, the fungal pathogen responsible for white-nose syndrome (WNS), on their bat host. However, little is known about these metal acquisition pathways in P. destructans. In this study, we report the characterization of the P. destructans high-affinity copper transporter VC83_00191 (PdCTR1a), which is implicated as a virulence factor associated with the WNS disease state. Using Saccharomyces cerevisiae as a recombinant expression host, we find that PdCTR1a can efficiently traffic Cu ions into the yeast cytoplasm. Complementary studies in the native P. destructans fungus provide evidence that PdCTR1a transcripts and protein levels are dictated by Cu-bioavailability in the growth media. Our study demonstrates that PdCTR1a is a functional high-affinity copper transporter and is relevant to Cu homeostasis pathways in P. destructans.

Multiple direct and indirect roles of the Paf1 complex in transcription elongation, splicing, and histone modifications.

The polymerase-associated factor 1 (Paf1) complex (Paf1C) is a conserved protein complex with critical functions during eukaryotic transcription. Previous studies showed that Paf1C is multi-functional, controlling specific aspects of transcription ranging from RNA polymerase II (RNAPII) processivity to histone modifications. However, it is unclear how specific Paf1C subunits directly impact transcription and coupled processes. We have compared conditional depletion to steady-state deletion for each Paf1C subunit to determine the direct and indirect contributions to gene expression in Saccharomyces cerevisiae. Using nascent transcript sequencing, RNAPII profiling, and modeling of transcription elongation dynamics, we have demonstrated direct effects of Paf1C subunits on RNAPII processivity and elongation rate and indirect effects on transcript splicing and repression of antisense transcripts. Further, our results suggest that the direct transcriptional effects of Paf1C cannot be readily assigned to any particular histone modification. This work comprehensively analyzes both the immediate and the extended roles of each Paf1C subunit in transcription elongation and transcript regulation.

Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms, Clinical Management and Innovative Treatment.

With the continuous refinement of therapeutic measures, the survival rate of tumor patients has been improving year by year, while cardiovascular complications related to cancer therapy have become increasingly prominent. Exploring the mechanism and prevention strategy of cancer therapy-related cardiovascular toxicity (CTR-CVT) remains one of the research hotspots in the field of Cardio-Oncology in recent years. Cardiotoxicity of anticancer drugs involves heart failure, myocarditis, hypertension, arrhythmias and vascular toxicity, mechanistically related to vascular endothelial dysfunction, ferroptosis, mitochondrial dysfunction and oxidative stress. To address the cardiotoxicity induced by different anticancer drugs, various therapeutic measures have been put in place, such as reducing the accumulation of anticancer drugs, shifting to drugs with less cardiotoxicity, using cardioprotective drugs, and early detection. Due to the very limited treatments available to ameliorate anticancer drugs-induced cardiotoxicity, a few innovations are being shifted from animal studies to human studies. Examples include mitochondrial transplantation. Mitochondrial transplantation has been proven to be effective in in vivo and in vitro experiments. Several recent studies have demonstrated that intercellular mitochondrial transfer can ameliorate doxorubicin(DOX)-induced cardiotoxicity, laying the foundation for innovative therapies in anticancer drugs-induced cardiotoxicity. In this review, we will discuss the current status of anticancer drugs-induced cardiotoxicity in terms of the pathogenesis and treatment, with a focus on mitochondrial transplantation, and we hope that this review will bring some inspiration to you.

Novel CTR9 germline pathogenic splice site variant in siblings with Wilms tumor from Tanzania.

Wilms tumor is the most common childhood renal malignancy. Though mostly non-genetic, it can be syndromic with the involvement of many Wilms tumor predisposing genes and non-syndromic with the involvement of four genes: WT1, REST, TRIM28, and CTR9. Familial and bilateral Wilms tumors do occur, but these are rare. So far, four Wilms tumor families with pathogenic variants in the CTR9 gene have been described, all (presumably) inherited from unaffected fathers, and three leading to deletion of exon 9. We are reporting female siblings, of whom one has a bilateral Wilms tumor, with a novel pathogenic splice site variant in the CTR9 gene, leading to deletion of exon 9, and inherited from their asymptomatic father. The loss of heterozygosity in the tumor was confirmed. In conclusion, CTR9 pathogenic variants are a very rare cause of Wilms tumors and typically result in familial Wilms tumors.

Ctr9 promotes virulence of Candida albicans by regulating methionine metabolism.

Candida albicans, a part of normal flora, is an opportunistic fungal pathogen and causes severe health issues in immunocompromised patients. Its pathogenicity is intricately linked to the transcriptional regulation of its metabolic pathways. Paf1 complex (Paf1C) is a crucial transcriptional regulator that is highly conserved in eukaryotes. The objective of this study was to explore the role of Paf1C in the metabolic pathways and how it influences the pathogenicity of C. albicans. Paf1C knockout mutant strains of C. albicans (ctr9Δ/Δ, leo1Δ/Δ, and cdc73Δ/Δ) were generated using the CRISPR-Cas9 system. To investigate the effect of Paf1C on pathogenicity, macrophage interaction assays and mouse survival tests were conducted. The growth patterns of the Paf1C knockout mutants were analyzed through spotting assays and growth curve measurements. Transcriptome analysis was conducted under yeast conditions (30°C without serum) and hyphal conditions (37°C with 10% FBS), to further elucidate the role of Paf1C in the pathogenicity of C. albicans. CTR9 deletion resulted in the attenuation of C. albicans virulence, in macrophage and mouse models. Furthermore, we confirmed that the reduced virulence of the ctr9Δ/Δ mutant can be attributed to a decrease in C. albicans cell abundance. Moreover, transcriptome analysis revealed that metabolic processes required for cell proliferation are impaired in ctr9Δ/Δ mutant. Notably, CTR9 deletion led to the downregulation of methionine biosynthetic genes and the cAMP-PKA signaling pathway-related hypha essential genes, which are pivotal for virulence. Our results suggest that Ctr9-regulated methionine metabolism is a crucial factor for determining C. albicans pathogenicity.

Decreased spinal cord motor neuron numbers in mice depleted of central nervous system copper.

Disrupted copper availability in the central nervous system (CNS) is implicated as a significant feature of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Solute carrier family 31 member 1 (Slc31a1; Ctr1) governs copper uptake in mammalian cells and mutations affecting Slc31a1 are associated with severe neurological abnormalities. Here, we examined the impact of decreased CNS copper caused by ubiquitous heterozygosity for functional Slc31a1 on spinal cord motor neurons in Slc31a1+/- mice. Congruent with the CNS being relatively susceptible to disrupted copper availability, brain and spinal cord tissue from Slc31a1+/- mice contained significantly less copper than wild-type littermates, even though copper levels in other tissues were unaffected. Slc31a1+/- mice had less spinal cord α-motor neurons compared to wild-type littermates, but they did not develop any overt physical signs of motor impairment. By contrast, ALS model SOD1G37R mice had fewer α-motor neurons than control mice and exhibited clear signs of motor function impairment. With the expression of Slc31a1 notwithstanding, spinal cord expression of genes related to copper handling revealed only minor differences between Slc31a1+/- and wild-type mice. This contrasted with SOD1G37R mice where changes in the expression of copper handling genes were pronounced. Similarly, the expression of genes related to toxic glial activation was unchanged in spinal cords from Slc31a1+/- mice but highly upregulated in SOD1G37R mice. Together, results from the Slc31a1+/- mice and SOD1G37R mice indicate that although depleted CNS copper has a significant impact on spinal cord motor neuron numbers, the manifestation of overt ALS-like motor impairment requires additional factors.

Characterization of a High-Affinity Copper Transporter in the White-Nose Syndrome Causing Fungal Pathogen Pseudogymnoascus destructans.

Copper is an essential micronutrient and the ability to scavenge tightly bound or trace levels of copper ions at the host-pathogen interface is vital for fungal proliferation in animal hosts. Recent studies suggest that trace metal ion acquisition is critical for the establishment and propagation of Pseudogymnoascus destructans, the fungal pathogen responsible for white-nose syndrome (WNS), on their bat host. However, little is known about these metal acquisition pathways in P. destructans. In this study, we report the characterization of the P. destructans high-affinity copper transporter VC83_00191 (PdCTR1a), which is implicated as a virulence factor associated with the WNS disease state. Using Saccharomyces cerevisiae as a recombinant expression host, we find that PdCTR1a localizes to the cell surface plasma membrane and can efficiently traffic Cu-ions into the yeast cytoplasm. Complementary studies in the native P. destructans fungus provide evidence that PdCTR1a transcripts and protein levels are dictated by Cu-bioavailability in the growth media. Our study demonstrates that PdCTR1a is a functional high-affinity copper transporter and is relevant to Cu-homeostasis pathways in P. destructans.

Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs.

Class B1 G protein-coupled receptors (GPCRs) are peptide hormone receptors and well validated therapeutic targets, however development of non-peptide drugs targeting this class of receptors is challenging. Recently, a series of isoquinoline-based derivates were reported in the patent literature as allosteric ligands for the glucagon receptor subfamily, and two compounds, LSN3451217 and LSN3556672, were used to facilitate structural studies with the glucagon-like peptide-1 receptor (GLP-1R) and glucose dependent insulinotropic peptide receptor (GIPR) bound to orthosteric agonists. Here we pharmacologically characterized stereoisomers of LSN3451217 and LSN3556672, across the class B1 GPCR family. This revealed LSN3556672 isomers are agonists for the glucagon receptor (GCGR), GLP-1R, GIPR and the calcitonin receptor (CTR), albeit the degree of agonism varied at each receptor. In contrast, LSN3451217 isomers were more selective agonists at the GLP-1R, with lower potency at the GCGR and CTR and no activity at the GIPR. All compounds also modulated peptide-mediated cyclic adenosine monophosphate (cAMP) signaling at the GIPR, and to a lesser extent the GLP-1R, in a probe-dependent manner, with modest positive allosteric modulation observed for some peptides, and negligible effects observed with other peptides. In contrast neutral or weak negative/positive allosteric modulation was observed with peptides assessed at the GCGR and CTR. This study expands our knowledge on class B1 GPCR allosteric modulation and may have implications for future structural and drug discovery efforts targeting the class B1 GPCR subfamily.

Protocol for a single-arm, multicenter, prospective, confirmatory phase III trial of wedge resection for invasive ground glass opacity-featured lung cancer with a size ≤2 cm and a consolidation tumor ratio between 0.25 and 0.5 (ECTOP-1020 study).

Background: Segmentectomy is the current standard treatment for ground glass opacity (GGO)-featured lung cancer patients with a tumor size ≤2 cm and a consolidation tumor ratio (CTR) between 0.25 and 0.5. However, compared with wedge resection, segmentectomy destroys the patient's hilar structure and consumes more lung parenchyma. A recent study demonstrated that wedge resection could yield comparable results for this group of patients. Methods: This study aimed to confirm the noninferiority of wedge resection over standard surgery in invasive GGO-featured lung cancer patients with a size ≤2 cm and a CTR between 0.25 and 0.5, as measured by 5-year overall survival (OS). The primary endpoint is 5-year OS. The secondary endpoints are 5-year recurrence-free survival (RFS), the R0 resection rate, pulmonary function, recurrence and metastasis sites, and adverse events after surgery. During the trial period, 286 patients are enrolled from six Chinese institutions. Discussion: The primary results of this study will be actively disseminated through manuscript publications and conference presentations. This prospective study will evaluate the surgical efficacy and safety of wedge resection for small (tumor size ≤2 cm with a CTR between 0.25 and 0.5) invasive GGO-featured lung cancer and will support the standardization of this surgical strategy. Trial Registration: This trial has been registered on ClinicalTrial.gov (No. NCT06102161).

Study on the expression regulation of the CTR1 gene in the ethylene signaling pathway.

The CONSTITUTIVE TRIPLERESPONSE1 (CTR1) is a crucial component in the ethylene signaling pathway. CTR1 transmits signals perceived by ethylene receptors to downstream EIN2 proteins through phosphorylation/dephosphorylation. Although some studies have explored the functions and mechanisms of CTR1, research on its expression and regulation remains relatively limited. This study investigates the tissue-specific expression of the Arabidopsis CTR1 gene and its expression and regulatory mechanisms under ethylene induction. Arabidopsis was treated with ethylene, and changes in CTR1 gene expression were detected using real-time quantitative PCR. The experimental results show that in rosette leaves of 28-day-old Arabidopsis, CTR1 expression is induced by ethylene. To investigate its molecular mechanism, the promoter sequence of the CTR1 was cloned and vectors were constructed by linking the promoter sequence with luciferase and GUS genes. Stable transgenic Arabidopsis lines were obtained, and promoter activity in these materials was analyzed. Promoter activity analysis confirmed that CTR1 promoter activity is ethylene-inducible and that this induction is dependent on the functions of proteins such as EIN2, EIN3, and EILs. Additionally, the study found that CTR1 expression is higher during seed germination and maintained at lower levels in mature leaves and plants. This study provides a detailed observation of CTR1 gene expression and, for the first time, identifies that the CTR1 promoter is regulated by ethylene induction, offering new options for designing ethylene signaling pathway reporter systems.

Measurement of Cardiothoracic Ratio on Chest X-rays Using Artificial Intelligence-A Systematic Review and Meta-Analysis.

Background: Chest X-rays (CXRs) are pivotal in clinical diagnostics, particularly in assessing cardiomegaly through the cardiothoracic ratio (CTR). This systematic review and meta-analysis evaluate the efficacy of artificial intelligence (AI) in automating CTR determination to enhance patient care and streamline diagnostic processes. They are concentrated on comparing the performance of AI models in determining the CTR against human assessments, identifying the most effective models for potential clinical implementation. This study was registered with PROSPERO (no. CRD42023437459). No funding was received. Methods: A comprehensive search of medical databases was conducted in June 2023. The search strategy adhered to the PICO framework. Inclusion criteria encompassed original articles from the last decade focusing on AI-assisted CTR assessment from standing-position CXRs. Exclusion criteria included systematic reviews, meta-analyses, conference abstracts, paediatric studies, non-original articles, and studies using imaging techniques other than X-rays. After initial screening, 117 articles were reviewed, with 14 studies meeting the final inclusion criteria. Data extraction was performed by three independent investigators, and quality assessment followed PRISMA 2020 guidelines, using tools such as the JBI Checklist, AMSTAR 2, and CASP Diagnostic Study Checklist. Risk of bias was assessed according to the Cochrane Handbook guidelines. Results: Fourteen studies, comprising a total of 70,472 CXR images, met the inclusion criteria. Various AI models were evaluated, with differences in dataset characteristics and AI technology used. Common preprocessing techniques included resizing and normalization. The pooled AUC for cardiomegaly detection was 0.959 (95% CI 0.944-0.975). The pooled standardized mean difference for CTR measurement was 0.0353 (95% CI 0.147-0.0760). Significant heterogeneity was found between studies (I2 89.97%, p < 0.0001), with no publication bias detected. Conclusions: Standardizing methodologies is crucial to avoid interpretational errors and advance AI in medical imaging diagnostics. Uniform reporting standards are essential for the further development of AI in CTR measurement and broader medical imaging applications.

Endoscopic Versus Open Treatment of Carpal Tunnel Syndrome: Postoperative Complications in Patients With Diabetes Mellitus.

Purpose: Patients with type 2 diabetes mellitus (T2DM) often face higher postoperative complication rates. Limited data exist regarding outcomes in T2DM patients undergoing carpal tunnel release (CTR). This study compares complication rates between endoscopic CTR (ECTR) and open CTR (OCTR) in patients with T2DM. Methods: The TriNetX database was used to perform a retrospective cohort study of 67,225 patients with T2DM who underwent ECTR (n = 17,792) or OCTR (n = 49,433). Demographic data, medical comorbidities, and complication rates were analyzed. A 1:1 propensity score match was performed to calculate risk ratios and 95% confidence intervals of postoperative median nerve injury, 6-week wound dehiscence, and 6-week wound infection. Results: After matching, a significantly greater number of ECTR patients had liver disease (P = <.001) and a body mass index > 40 (P = .001) compared to the OCTR group. These patients also had a lower incidence of fluid and electrolyte disorders (P = .003). Patients with T2DM who underwent ECTR had a significantly lower relative risk of 6-week wound infection, 6-week wound dehiscence, and median nerve injury (all P < .001) compared to patients who underwent OCTR. Conclusions: In our analysis of T2DM patients undergoing CTR, ECTR yielded significantly lower rates of wound infection, wound dehiscence, and nerve injury within 6-weeks post-surgery, reducing the risk by 43%, 52%, and 58%, respectively. These findings suggest that ECTR may result in a lower complication rate in this patient population. Type of study/level of evidence: III.

Technological Developments, Exercise Training Programs, and Clinical Outcomes in Cardiac Telerehabilitation in the Last Ten Years: A Systematic Review.

BACKGROUND: Cardiovascular diseases (CVDs) are associated with very high rates of re-hospitalization and mortality worldwide, so the complexity of these pathologies requires frequent access to hospital facilities. The guidelines also emphasize the importance of cardiac rehabilitation (CR) programs, which have demonstrated a favorable effect on outcomes, and cardiac telerehabilitation (CTR) could represent an innovative healthcare delivery model. The aim of our review is to study how technologies used in rehabilitation have changed over time and also to understand what types of rehabilitation programs have been used in telerehabilitation. METHODS: We searched randomized controlled trials (RCTs) in three electronic databases, PubMed, Web of Science, and Scopus, from January 2015 to January 2024, using relevant keywords. Initially, 502 articles were found, and 79 duplicates were identified and eliminated with EndNote. RESULTS: In total, 16 RCTs fulfilled the pre-defined criteria, which were analyzed in our systematic review. The results showed that after CTR, there was a significant improvement in main outcome measures, as well as in relation to technological advances. CONCLUSIONS: Moreover, compared to center-based rehabilitation, CTR can offer further advantages, with better cost-effectiveness, the breakdown of geographical barriers, and the improvement of access to treatment for the female population, which is traditionally more socially committed.

Design and characterization of a hybrid PET detector with DOI capability.

BACKGROUND: Monolithic or semi-monolithic detectors are attractive for positron emission tomography (PET) scanners with depth-of-interaction (DOI) capability. However, they often require complicated calibrations to determine the interaction positions of gamma photons. PURPOSE: We introduce a novel hybrid detector design that combines pixelated and semi-monolithic elements to achieve DOI capability while simplifying the calibrations for positioning. METHODS: A prototype detector with eight hybrid lutetium-yttrium oxyorthosilicate (LYSO) layers having dimensions of 25.8 × 12.9 × 15 mm3 was constructed. The energy-weighted and energy-squared weighted averages were used for estimating the x- (pixelated direction) and y-positions (non-pixelated direction). Pseudo-pixels were defined as discrete areas on the flood image based on the crystal look-up table (LUT). The intrinsic spatial resolutions in the pixelated and non-pixelated directions were measured. The ratio of the maximum to the sum of the multipixel photon counter (MPPC) signals was used to estimate the DOI positions. The coincidence timing resolution (CTR) was measured using the average and energy-weighted average of the earliest n time stamps. Two energy windows of 250-700 and 400-600 keV were applied for the measurements. RESULTS: The pattern of the flood images showed discrete event clusters, demonstrating that simple calibrations for determining the x- and y-positions of events could be achieved. Under 400-600 keV energy window, the average intrinsic spatial resolutions were 1.15 and 1.34 mm for the pixelated and non-pixelated directions; the average DOI resolution of the second row of pseudo-pixels was 5.1 mm in full width at half maximum (FWHM); when using the energy-weighted average of the earliest four-time stamps, the best CTR of 350 ps was achieved. Applying a broader energy window of 250-700 keV only slightly degrades the DOI resolution while maintaining the intrinsic resolution; the best CTR degrades to 410 ps. CONCLUSIONS: The proposed hybrid detector concept was verified, and a prototype detector showed high performance for 3D positioning and timing resolution. The novel detector concept shows promise for preclinical and clinical PET scanners with DOI capability.

Holistic evaluation of a machine learning-based timing calibration for PET detectors under varying data sparsity.

Objective.Modern PET scanners offer precise TOF information, improving the SNR of the reconstructed images. Timing calibrations are performed to reduce the worsening effects of the system components and provide valuable TOF information. Traditional calibration procedures often provide static or linear corrections, with the drawback that higher-order skews or event-to-event corrections are not addressed. Novel research demonstrated significant improvements in the reachable timing resolutions when combining conventional calibration approaches with machine learning, with the disadvantage of extensive calibration times infeasible for a clinical application. In this work, we made the first steps towards an in-system application and analyzed the effects of varying data sparsity on a machine learning timing calibration, aiming to accelerate the calibration time. Furthermore, we demonstrated the versatility of our calibration concept by applying the procedure for the first time to analog readout technology.Approach.We modified experimentally acquired calibration data used for training regarding their statistical and spatial sparsity, mimicking reduced measurement time and variability of the training data. Trained models were tested on unseen test data, characterized by fine spatial sampling and rich statistics. In total, 80 decision tree models with the same hyperparameter settings, were trained and holistically evaluated regarding data scientific, physics-based, and PET-based quality criteria.Main results.The calibration procedure can be heavily reduced from several days to some minutes without sacrificing quality and still significantly improving the timing resolution from(304±5)psto(216±1)pscompared to conventionally used analytical calibration methods.Significance.This work serves as the first step in making the developed machine learning-based calibration suitable for an in-system application to profit from the method's capabilities on the system level. Furthermore, this work demonstrates the functionality of the methodology on detectors using analog readout technology. The proposed holistic evaluation criteria here serve as a guideline for future evaluations of machine learning-based calibration approaches.

Radiographic and echocardiographic evaluation in rescued Korean raccoon dogs (Nyctereutes procyonoides koreensis).

Introduction: Nyctereutes procyonoides koreensis (Korean raccoon dog), a member of the Canidae family, is anatomically similar to dogs. Previous studies have used vertebral heart scale measurements to measure the cardiac size of Korean raccoon dogs on thoracic radiographs; however, the use of additional cardiac size indices, such as vertebral left arial score, intercostal space, cardiothoracic ratio, and echocardiographic indices, has not been reported. Therefore, this study aimed to establish normal reference ranges for various thoracic radiographic and echocardiographic indices in normal Korean raccoon dogs. Methods: Twenty-six Korean raccoon dogs (11 males and 15 females) were included in this study. The thoracic radiographic indices, vertebral heart scale score, and vertebral left atrial score were measured in the right lateral view. The intercostal space and cardiothoracic ratio were measured in the ventrodorsal view. The echocardiograms were evaluated in the right parasternal long and short axis view and left parasternal apical view. Results: The mean values for the thoracic radiographic and echocardiographic indices were as follows: vertebral heart scale, 9.12 ± 0.74; vertebral left atrial score, 1.5 ± 0.31; intercostal spaces, 3.17 ± 0.34; cardiothoracic ratio, 0.69 ± 0.07; left atrial to aortic root ratio, 1.22 ± 0.14; main pulmonary artery to aorta ratio, 1.22 ± 0.14; left ventricular end-diastolic internal diameter normalized for body weight, 1.36 ± 0.19; end-diastolic volume index, 51.07 ± 19.6; end-systolic volume index, 16.54 ± 7.45; the peak velocity of early diastolic transmitral flow, 73.13 ± 15.46 cm/s; and the ratio between the transmitral flow velocities and the peak early diastolic velocity, 1.77 ± 0.47. Only percent increase in the left ventricular end-systolic internal diameter was negatively correlated with body weight. The remaining indices showed no correlations with body weight. Conclusion: To the best of our knowledge, this is the first case report covering both thoracic radiographic and endocardiographic indices for Korean raccoon dogs. Thus, the thoracic radiographic and echocardiographic indices established in this study may be used to evaluate the cardiac condition of Korean raccoon dogs.

Maximum surgical blood ordering schedule for elective surgical procedures in Omdurman teaching hospital, Sudan.

BACKGROUND: The need for blood during a surgical procedure is greater than what blood banks are able to provide. There is an excessive amount of blood being ordered for elective surgeries, surpassing the actual requirements. Only 30% of the cross matched blood is actually used in these surgeries. The accuracy of estimating the transfusion needs before a surgical procedure can be determined by looking at the cross match to transfusion ratio and the transfusion index. "These indicators play a crucial role in developing the maximum surgical blood ordering schedule; in this study, these indicators were tested." AIM OF STUDY: Is to determine the efficiency of blood ordering and transfusion practices for patients undergoing elective surgeries. METHODS: This study is a prospective cross-sectional hospital-based study done at Omdurman Teaching Hospital-Sudan. Conducted for the duration of 6 months period from July to December 2019.The study participants were patients who underwent elective surgical procedures in general surgery and Urology departments as total coverage sample over a period of study duration. Ethical clearance obtained from ethical committee of Sudan Medical Specialization Board. RESULTS: Two hundreds seven patients included in this study, the amount of blood units requested were 443-unit, cross matching for 98.6% (n 437) of units were done. Only 100 unit were Transfused (22,8%). The calculated CT ratio was 4.4, transfusion index was 1.6 and transfusion probability was 29.9%. CONCLUSION: Transfusion probability and transfusion index of the present study were optimal but comparatively higher than the standard guidelines as most of the cross matched blood was not utilized.

CTR > 0.7 predicts the subgroup of lung adenocarcinomas ≤ 2 cm at risk of poor outcome treated by sublobar resection compared to lobar resection.

BACKGROUND: A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. METHODS: A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. RESULTS: In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P < 0.001), age > 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR<0.7, 0.7 ≤ CTR<1, and CTR = 1.The lobar resection groups had more favorable clinical outcomes than the sublobar resection groups in both the 0.7 ≤ CTR < 1(RFS: P < 0.001, OS: P = 0.001) and CTR = 1(RFS: P = 0.001, OS: P = 0.125). However, for patients with 0 ≤ CTR < 0.7, no difference in either RFS or OS was found between the lobar resection and sublobar resection groups, all of which had no positive events. Patients with a CTR between 0.7 and 1 who underwent lobar resection had similar 5-year RFS and OS rates compared to those with a CTR between 0 and 0.7 who underwent sublobar resection (100% vs. 100%). Nevertheless, a CTR of 1 following lobar resection resulted in notably reduced RFS and OS when compared to a CTR between 0.7 and 1 following lobar resection (P = 0.005 and P = 0.016, respectively). CONCLUSION: Lobar resection is associated with better long-term survival outcomes than sublobar resection for small lung adenocarcinomas ≤ 2 cm and CTR ≥ 0.7.