Circulating soluble CD163 is associated with reduced Glasgow Coma Scale Score and 1-year all-cause mortality in traumatized patients.

Soluble CD163 (sCD163) is a biomarker of macrophage activation, not previously investigated in the circulation of traumatized patients. A biobank of 398 adult trauma patients was analyzed. Patients with an Injury Severity Score (ISS) >8 served as trauma patients (n = 195) and those with ISS ≤8 as trauma controls (n = 203). Serum samples obtained upon admission, 15h and 72h after were analyzed for sCD163 using an in-house ELISA. Multiple linear regression was used to analyze the association between admission levels of sCD163 with, 1: overall trauma severity (ISS), and 2: severity of injury to specified organs using Abbreviated Injury Score (AIS) and Glasgow Coma Scale (GCS). The association between the peak level of sCD163 with 1-year all-cause mortality was analyzed by logistic regression analysis. Median admission levels of sCD163 were higher in trauma patients than trauma controls [2.32 (IQR 1.73 to 2.86) vs. 1.92 (IQR 1.41 to 2.51) mg/L, p < 0.01]. Worsening GCS score was associated with a 10.3% (95% CI: 17.0 to 3.1, p < 0.01) increase in sCD163. Increasing Head-AIS score was associated with a 5.1% (95% CI: -0.5 to 11.0, p = 0.07) increase in sCD163. The remaining AIS scores and ISS were not consistently associated with sCD163 admission levels. Each mg/L increase in sCD163 peak level had an odds ratio 1.34 (95%CI: 0.98 to 1.83), p = 0.06) after adjustment for age, sex, and GCS. Circulating sCD163 is increased in traumatized patients and associated with worsening GCS. Our findings suggest an association between circulating sCD163 levels with 1-year all-cause mortality.

Search for Strange Quark Matter and Nuclearites on Board the International Space Station (SQM-ISS): A Future Detector to Search for Massive, Non-Relativistic Objects in Space.

SQM-ISS is a detector that will search from the International Space Station for massive particles possibly present among the cosmic rays. Among them, we mention strange quark matter, Q-Balls, lumps of fermionic exotic compact stars, Primordial Black Holes, mirror matter, Fermi balls, etc. These compact, dense objects would be much heavier than normal nuclei, have velocities of galaxy-bound systems, and would be deeply penetrating. The detector is based on a stack of scintillator and piezoelectric elements which can provide information on both the charge state and mass, with the additional timing information allowing to determine the speed of the particle, searching for particles with velocities of the order of galactic rotation speed (v ≲ 250 km/s). In this work, we describe the apparatus and its observational capabilities.

Prognostic value of the "dynamic" R2-ISS in patients with multiple myeloma undergoing anti-CD38 antibody-based triplet therapies.

To retrospectively analyze whether the second revision of the international staging system (R2-ISS) influenced prognosis at treatment initiation in patients with multiple myeloma (MM) receiving anti-CD38 antibody-based triplet treatments. High-risk chromosomal abnormalities were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at the initiation of treatment and defined as "dynamic R2-ISS." Data from 150 patients who underwent the defined treatments were analyzed. The median progression-free survival (PFS) was 19.5 months, and the median overall survival (OS) was 36.5 months. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS. The median PFS for patients with dynamic R2-ISS IV was 3.3 months, and the median OS was 11.7 months, indicating extremely poor outcomes. Although the Revised International Staging System (R-ISS) calculated at the initiation of treatment significantly stratified treatment outcomes, the patients classified as R-ISS could be further stratified by R2-ISS to provide better prognostic information. Dynamic R2-ISS showed potential as a prognostic tool in patients with MM who are treated with anti-CD38 antibody-based triplet therapies.

R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Input-to-state stability of delayed memristor-based inertial neural networks via non-reduced order method.

This paper is concerned with the input-to-state stability (ISS) for a kind of delayed memristor-based inertial neural networks (DMINNs). Based on the nonsmooth analysis and stability theory, novel delay-dependent and delay-independent criteria on the ISS of DMINNs are obtained by constructing different Lyapunov functions. Moreover, compared with the reduced order approach used in the previous works, this paper consider the ISS of DMINNs via non-reduced order approach. Directly analysis the model of DMINNs can better maintain its physical backgrounds, which reduces the complexity of calculations and is more rigorous in practical application. Additionally, the novel proposed results on the ISS of DMINNs here incorporate and complement the existing studies on memristive neural network dynamical systems. Lastly, a numerical example is provided to show that the obtained criteria are reliable.

[Genome Stability of Bacillus velezensis after Two-Year Exposure in Open Space].

Spore-forming bacteria have a unique resistance to negative environmental conditions, including aggressive space factors, and are an excellent model for studying adaptation mechanisms and survival strategies at the molecular level. The study analyzed the genome of Bacillus velezensis, which remained viable after a 2-year exposure in outer space on the outer surface of the ISS as part of the Test space experiment. A comparative analysis of the draft genomes of the exhibit strain and the ground control did not reveal significant changes; the average nucleotide identity was 99.98%, which indicates the ability of microorganisms to maintain genome stability in space conditions, due to both increased stress resistance of bacterial spores and efficient operation of the system of repair of accumulated changes. The study of a single nucleotide polymorphism in the genome of B. velezensis revealed nine point substitutions, three of which are in intergenic regions, six in protein-coding genes, three of them are missense mutations, two nucleotide deletions leading to a shift in the reading frame, and one synonymous substitution. The profiles of the housekeeping genes were determined during MLST typing and it was found that the allelic profiles obtained for B. velezensis T15.2 and 924 strains do not correspond to any of the previously described sequence types. The presented results indicate the ability of B. velezensis bacteria to maintain the viability of spores and the integrity of the genome for a long time under extreme conditions of outer space, which is important for the problem of planetary protection, as well as the potential possibility of performing biotechnological processes based on B. velezensis during space exploration.

Prognostic Factors and Clinical Outcomes of Surgical Treatment of Major Thoracic Trauma.

BACKGROUND: Major thoracic trauma represents a life-threatening condition, requiring a prompt multidisciplinary approach and appropriate pathways for effective recovery. While acute morbidity and mortality are well-known outcomes in thoracic-traumatized patients, long-term quality of life in patients surviving surgical treatment has not been widely investigated before. METHODS: Between November 2016 and November 2023, thirty-two consecutive patients were operated on because of thoracic trauma. Age, sex, comorbidities, location and extent of thoracic trauma, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), Organ Injury Scale (OIS), intra and extrathoracic organ involvement, mechanism of injury, type of surgical procedure, postoperative complications, ICU and total length of stay, immediate clinical outcomes and long-term quality of life-by using the EQ-5D-3L scale and Numeric Rate Pain Score (NPRS)-were collected for each patient Results: Results indicated no significant difference in EQOL.5D3L among patients with thoracic trauma based on AIS (p = 0.55), but a significant difference was observed in relation to ISS (p = 0.000011). CONCLUSIONS: ISS is correlated with the EQOL.5D3L questionnaire on long-term quality of life, representing the best prognostic factor-in terms of long-term quality of life-in patients surviving major thoracic trauma surgical treatment.

Beyond the Slopes and Highways: Endovascular Repair of Blunt Traumatic Aortic Injuries after Skiing versus Motor Vehicle Accidents.

Background: Blunt traumatic aortic injury (BTAI) is a potentially fatal condition, typically resulting from high-velocity trauma. To date, little is known about this type of injury among skiers, who form the largest patient cohort with aortic injuries in the alpine region of Tyrol, Austria. Methods: This retrospective, single-center study at the University Hospital of Innsbruck analyzed patients who underwent endovascular treatment for blunt traumatic aortic injury from 2005 to 2023. Patient data were extracted from electronic and digitalized medical history records. Subsequent analyses compared the baseline characteristics and clinical results of the skiing accident (SA) group to the motor vehicle accident (MVA) group. Results: A total of 48 BTAI patients receiving TEVAR were included, 25 (52%) from SAs versus 23 (48%) from MVAs, who were predominantly male (92% vs. 78.3%). Despite similar preoperative risk profiles and ASA Scores (1.44 vs. 1.74) and no marked differences in BTAI injury grades or the affected aortic zones, significant disparities emerged: the SA group experienced shorter median ICU stays (3 vs. 11 days, p = 0.0007), fewer concomitant injuries (5 vs. 7, p = 0.005), and lower Injury Severity Scores (ISSs) (29 vs. 33, p = 0.003) than their MVA counterparts. The presence of rib fractures alongside other thoracic injuries, such as lung injury, pneumothorax, or hemothorax, was strongly correlated with BTAI in patients following skiing accidents (OR = 128.5). Conclusions: The injury severities and locations of BTAI in SA patients were comparable to those in MVA patients, indicating similar mechanisms of thoracic trauma. However, the SA patients experienced fewer concurrent pelvic and extremity fractures, had less post-procedural morbidity, and required shorter ICU stays. The presence of rib fractures combined with other thoracic injuries strongly suggests BTAI. These indicators should lead to prompt imaging and appropriate therapy.

Pituitary MRI Radiomics Improves Diagnostic Performance of Growth Hormone Deficiency in Children Short Stature: A Multicenter Radiomics Study.

RATIONALE AND OBJECTIVES: To develop an efficient machine-learning model using pituitary MRI radiomics and clinical data to differentiate growth hormone deficiency (GHD) from idiopathic short stature (ISS), making the diagnostic process more acceptable to patients and their families. MATERIALS AND METHODS: A retrospective cohort of 297 GHD and 300 ISS children (4-12 years) were enrolled as training and validation cohorts (8:2 ratio). An external cohort from another institution (49 GHD and 51 ISS) was employed as the testing cohort. Radiomics features extracted from the anterior pituitary gland on sagittal T1-weighted image (1.5 T or 3.0 T) were used to develop a radiomics model after feature selection. Hematological biomarkers were selected to create a clinical model and combine with the optimal radiomics features to create a clinical-radiomics model. The area under the receive operating characteristic curve (AUC) and Delong test compared the diagnostic performance of the previously mentioned three models across different validation and testing cohorts. RESULTS: 17 radiomics features were selected for the radiomics model, and total protein, total cholesterol, free triiodothyronine, and triglyceride were utilized for the clinical model. In the training and validation cohorts, the diagnostic performance of the clinical-radiomics model (AUC=0.820 and 0.801) was comparable to the radiomics model (AUC=0.812 and 0.779, both P >0.05), both outperforming the clinical model (AUC=0.575 and 0.593, P <0.001). In the testing cohort, the clinical-radiomics model exhibited the highest AUC of 0.762 than the clinical and radiomics model (AUC=0.604 and 0.741, respectively, P <0.05). In addition, the clinical and radiomics models demonstrated similar diagnostic performance in the testing cohort (P >0.05). CONCLUSION: Integrating radiomics features from conventional pituitary MRI with clinical indicators offers a minimally invasive approach for identifying GHD and shows robustness in a multicenter setting.

Association of red blood cell distribution width with mortality among multiple trauma patients.

Background: Identifying the severity of trauma to provide timely and adequate treatment and predict the prognosis are some of the significant challenges in trauma management. Increased red blood cell distribution width (RDW) is associated with several pathologies and associated mortality. This study aims to evaluate the RDW in predicting 24 h and 30-day mortality among multiple trauma patients. Methods: In this retrospective study, multiple trauma patients with ISS ≤16 were included. Blood samples of the patients were collected at 1 h and 24 h of the referral to determine RDW. Demographic data, 24 h and 30-day mortality, injury severity score (ISS), and RDW outcomes were evaluated for all the patients. Results: Of the 300 patients included in the study, 52 patients died in the first 24 h, and 85 patients within 30 days. One hour and 24 h RDW were not significantly different in 30-day mortality patients, P=0.104 and P=0.156, respectively. RDW in 30-day mortality patients was not significantly different at 1 h and 24 h, P-value=0.875. The means ISS in 24 h, 30-day mortality and survivors was significantly different, P<0.001. Conclusion: Our study does not report a significant increase in RDW among 24 h and 30-day mortality and survivor patients. ISS was significantly different among the two groups.

Amorphous calcium carbonate enhances osteogenic differentiation and myotube formation of human bone marrow derived mesenchymal stem cells and primary skeletal muscle cells under microgravity conditions.

Astronauts are exposed to severely stressful physiological conditions due to microgravity and increased space radiation. Space environment affects every organ and cell in the body and the significant adverse effects of long-term weightlessness include muscle atrophy and deterioration of the skeleton (spaceflight osteopenia). Amorphous Calcium Carbonate (ACC) emerges as a promising candidate for prevention of these effects, owing to its unique physicochemical properties and its potential to address the intricately linked nature of bone-muscle crosstalk. Reported here are two studies carried out on the International Space Station (ISS). The first, performed in 2018 as a part of the Ramon-Spacelab project, was a preliminary experiment, in which stromal murine cells were differentiated into osteoblasts when ACC was added to the culture medium. A parallel experiment was done on Earth as a control. The second study was part of Axiom-1's Rakia project mission launched to the ISS on 2022 utilizing organ-on-a-chip methodology with a specially designed autonomous module. In this experiment, human bone-marrow derived mesenchymal stem cells (hBM-MSCs) and human primary muscle cells were cultured in the presence or absence of ACC, in duplicates. The results showed that ACC enhanced differentiation of human primary skeletal muscle cells into myotubes. Similarly, hBM-MSCs were differentiated significantly better into osteocytes in the presence of ACC leading to increased calcium deposits. The results, combined with previous data, support the use of ACC as an advantageous supplement for preventing muscle and bone deterioration in outer space conditions, facilitating extended extraterrestrial voyages and colonization.

Automatic measurements with the Pille-ISS thermoluminescent dosimeter system on board the International Space Station (2003-2021).

The health risk of staying in space is a well-known fact, and the radiation doses to the astronauts must be monitored. The Pille-ISS thermoluminescent dosimeter system is present on the International Space Station (ISS) since 2003. We present an analysis of 60000 data points over 19 years from the 90 min automatic measurements and show a 4-day-long segment of 15 min measurements. In the case of the 15 min we show that the mapping of the radiation environment for the orbit of the ISS is possible with the Pille system. From our results the dose rates inside the South Atlantic Anomaly (SAA) are at least 1 magnitude higher than outside. From the 90 min data, we select orbits passing through the SAA. A statistical correlation in the SAA between the ISS altitude and monthly mean dose rate is presented with the Spearman correlation value of ρSAA=0.56. The dose rate and the sunspot number show strong inverse Pearson correlation (R2=-0.90) at a given altitude.

The application of electrical impedance tomography and surgical outcomes of thoracoscope-assisted surgical stabilization of rib fractures in severe chest trauma.

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p < 0.001). In patients with major thoracic injury, older age and higher injury survival scale account for higher mortality rate. Effective surgical stabilization of rib fractures shortened the ICU stay and helped achieve better performance in EIT. Thoracoscope-assisted rib fixation is suggested in severe trauma cases.

Risk stratification in multiple myeloma: Are we there yet?

The second revision of international staging system (R2-ISS) shows promise in patients with multiple myeloma treated with a regimen of novel agent-based induction therapy, autologous stem cell transplant and maintenance therapy, but challenges persist. This study by Alzahrani et al. underscores the importance of refining risk assessment tools for tailored treatment strategies. Commentary on: Alzahrani et al. Impact of revised international staging system 2 (R2-ISS) risk stratification on outcomes of patients with multiple myeloma receiving autologous hematopoietic stem cell transplantation. Br J Haematol 2024;204:1944-1952.

Employing optical lightning data to identify lightning flashes associated to terrestrial gamma-ray flashes.

Terrestrial gamma-ray flashes (TGFs) are bursts of energetic X- and gamma-rays emitted from thunderstorms. The Atmosphere-Space Interactions Monitor (ASIM) mounted onto the International Space Station (ISS) is dedicated to measure TGFs and optical signatures of lightning; ISS LIS (Lightning Imaging Sensor) detects lightning flashes allowing for simultaneous measurements with ASIM. Whilst ASIM measures ∼300-400 TGFs per year, ISS LIS detects ∼106 annual lightning flashes giving a disproportion of four orders of magnitude. Based on the temporal evolution of lightning flashes and the spatial pattern of the constituing events, we present an algorithm to reduce the number of space-detected flashes potentially associated with TGFs by ∼ 60% and of associated LIS groups by ∼ 95%. We use ASIM measurements to confirm that the resulting flashes are indeed those associated with TGFs detected at approx. 400 km altitude and thus benchmark our algorithm preserving 70-80% of TGFs from concurrent ASIM-LIS measurements. We compare how the radiance, footprint size and the global distribution of lightning flashes of the reduced set relates to the average of all measured lightning flashes and do not observe any significant difference. Finally, we present a parameter study of our algorithm and discuss which parameters can be tweaked to maximize the reduction efficiency whilst keeping flashes associated to TGFs. In the future, this algorithm will hence be capable of facilitating the search for TGFs in a reduced set of lightning flashes measured from space.

Genomic, functional, and metabolic enhancements in multidrug-resistant Enterobacter bugandensis facilitating its persistence and succession in the International Space Station.

BACKGROUND: The International Space Station (ISS) stands as a testament to human achievement in space exploration. Despite its highly controlled environment, characterised by microgravity, increased CO 2 levels, and elevated solar radiation, microorganisms occupy a unique niche. These microbial inhabitants play a significant role in influencing the health and well-being of astronauts on board. One microorganism of particular interest in our study is Enterobacter bugandensis, primarily found in clinical specimens including the human gastrointestinal tract, and also reported to possess pathogenic traits, leading to a plethora of infections. RESULTS: Distinct from their Earth counterparts, ISS E. bugandensis strains have exhibited resistance mechanisms that categorise them within the ESKAPE pathogen group, a collection of pathogens recognised for their formidable resistance to antimicrobial treatments. During the 2-year Microbial Tracking 1 mission, 13 strains of multidrug-resistant E. bugandensis were isolated from various locations within the ISS. We have carried out a comprehensive study to understand the genomic intricacies of ISS-derived E. bugandensis in comparison to terrestrial strains, with a keen focus on those associated with clinical infections. We unravel the evolutionary trajectories of pivotal genes, especially those contributing to functional adaptations and potential antimicrobial resistance. A hypothesis central to our study was that the singular nature of the stresses of the space environment, distinct from any on Earth, could be driving these genomic adaptations. Extending our investigation, we meticulously mapped the prevalence and distribution of E. bugandensis across the ISS over time. This temporal analysis provided insights into the persistence, succession, and potential patterns of colonisation of E. bugandensis in space. Furthermore, by leveraging advanced analytical techniques, including metabolic modelling, we delved into the coexisting microbial communities alongside E. bugandensis in the ISS across multiple missions and spatial locations. This exploration revealed intricate microbial interactions, offering a window into the microbial ecosystem dynamics within the ISS. CONCLUSIONS: Our comprehensive analysis illuminated not only the ways these interactions sculpt microbial diversity but also the factors that might contribute to the potential dominance and succession of E. bugandensis within the ISS environment. The implications of these findings are twofold. Firstly, they shed light on microbial behaviour, adaptation, and evolution in extreme, isolated environments. Secondly, they underscore the need for robust preventive measures, ensuring the health and safety of astronauts by mitigating risks associated with potential pathogenic threats. Video Abstract.

Determining information system end-user satisfaction and continuance intension with a unified modeling approach.

With the different characters of datatypes and large amount of data going to be managed in open-source database, localization to the specific linguistics is the major concern in Ethiopia, as the nation used different datatypes compared to the Gregorian systems. In this regard Amharic localization in open-source database can handle the difficulties in managing data for governmental and non-governmental organizations. Amharic Extension Module was introduced to governmental organizations for the data management capabilities. But, there is no research that can explore the system's quality, the users' satisfaction and intension of continuance of Amharic Extension Module from the perspective of both computer literates and illiterates. Therefore, this research work attempt or try to empirically examine and analyze the system quality, the users' satisfaction and intension of continuance of Amharic Extension Module from the perspective of all users in POESSA The major purpose/aim of this study/research is to brand or make up the research break/gap in the area of localization specific to the Amharic locals, and to show the implication of the practical and theoretical way based on the results of the research. For this purpose, questionnaires were used for the collection of the research data. A total of 395 copies of the questionnaires were distributed and 385 of them are collected without any problem from the organization indicated herewith. The statistical analysis tools such as SPSS and AMOS, and methods such as Structural equation model were used for the analysis of the research data. The results of the research recommended and suggested that system quality can significantly influence confirmation. Meanwhile, confirmation can directly and significantly influence perceived usefulness, performance expectations, and satisfaction. Additionally, performance expectation, perceived usefulness and confirmation can significantly impact/influence satisfaction. The satisfaction directly and most importantly and significantly influences the continuance intension. Finally, the research delivers/provides a concert indication for the legitimacy and validity of the integrated and combined models of UTUAT, ECTM, and D&M ISS in the field of localizations which can be a hypothetical and theoretical foundation for Amharic Extension Module-AEM users' and services of it.

VAS1-mediated nitrogen reshuffling in aromatic amino acid homeostasis.

Aromatic amino acids (AAAs) are essential for synthesis of proteins and numerous plant natural products, yet how plants maintain AAA homeostasis remains poorly understood. Wu et al. reported that the aminotransferase VAS1 plays a role in AAA homeostasis by transferring nitrogen from AAAs to non-proteinogenic amino acids, 3-carboxytyrosine and 3-carboxyphenylalanine.

Freesurfer Software Update Significantly Impacts Striatal Volumes in the Huntington's Disease Young Adult Study and Will Influence HD-ISS Staging.

Background: The Huntington's Disease Integrated Staging System (HD-ISS) defined disease onset using volumetric cut-offs for caudate and putamen derived from FreeSurfer 6 (FS6). The impact of the latest software update (FS7) on volumes remains unknown. The Huntington's Disease Young Adult Study (HD-YAS) is appropriately positioned to explore differences in FS bias when detecting early atrophy. Objective: Explore the relationships and differences between raw caudate and putamen volumes, calculated total intracranial volumes (cTICV), and adjusted caudate and putamen volumes, derived from FS6 and FS7, in HD-YAS. Methods: Images from 123 participants were segmented and quality controlled. Relationships and differences between volumes were explored using intraclass correlation (ICC) and Bland-Altman analysis. Results: Across the whole cohort, ICC for raw caudate and putamen was 0.99, cTICV 0.93, adjusted caudate 0.87, and adjusted putamen 0.86 (all p < 0.0005). Compared to FS6, FS7 calculated: i) larger raw caudate (+0.8%, p < 0.00005) and putamen (+1.9%, p < 0.00005), with greater difference for larger volumes; and ii) smaller cTICV (-5.1%, p < 0.00005), with greater difference for smaller volumes. The systematic and proportional difference in cTICV was greater than raw volumes. When raw volumes were adjusted for cTICV, these effects compounded (adjusted caudate +7.0%, p < 0.00005; adjusted putamen +8.2%, p < 0.00005), with greater difference for larger volumes. Conclusions: As new software is released, it is critical that biases are explored since differences have the potential to significantly alter the findings of HD trials. Until conversion factors are defined, the HD-ISS must be applied using FS6. This should be incorporated into the HD-ISS online calculator.