Merging High-Pressure Syngas Metal Catalysis and Biocatalysis in Tandem One-Pot Processes for the Synthesis of Non-chiral and Chiral Alcohols from Alkenes in Water.

While simultaneously proceeding reactions are among the most fascinating features of biosynthesis, this concept of tandem processes also offers high potential in the chemical industry in terms of less waste production and improved process efficiency and sustainability. Although examples of one-pot chemoenzymatic syntheses exist, the combination of completely different reaction types is rare. In this work, we demonstrate that extreme "antipodes" of the "worlds of catalysis" such as syngas-based high-pressure hydroformylation and biocatalyzed reduction can be combined within a tandem­type one-pot process in water, which both play an outstanding role as individual reactions. No significant deactivation was found for either the biocatalyst or the chemocatalyst. A proof­of­concept for the one-pot process starting from 1-octene was established with >99% conversion and 80% isolated yield of the desired alcohol isomers. All necessary components for hydroformylation and biocatalysis were added to the reactor from the beginning. This concept has been extended to chiral products by conducting the hydroformylation of styrene and an enzymatic dynamic kinetic resolution in a tandem mode, leading to an excellent conversion of >99% and an enantiomeric ratio of 91:9 to (S)­2-phenylpropanol. The overall process runs in water under mild and energy-saving conditions, without any need for intermediate isolation.

Differential Effects of JAK1 vs. JAK2 Inhibition in Mouse Models of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of which signal via the JAK/STAT pathway. Indeed, the JAK1/2 inhibitor ruxolitinib has demonstrated efficacy in pre-clinical studies and early-phase clinical trials in HLH. Nevertheless, concerns remain for ruxolitinib-induced cytopenias, which are postulated to result from the blockade of JAK2-dependent hematopoietic growth factors. To explore the therapeutic effects of selective JAK inhibition in mouse models of HLH, we carried out studies incorporating the JAK1 inhibitor itacitinib, the JAK2 inhibitor fedratinib and the JAK1/2 inhibitor ruxolitinib. All three drugs were well-tolerated and at the doses tested, they suppressed interferon-gamma (IFNg)-induced STAT1 phosphorylation in vitro and in vivo. Itacitinib, but not fedratinib, significantly improved survival and clinical scores in CpG-induced secondary HLH. Conversely, in primary HLH, where perforin-deficient (Prf1-/-) mice are infected with lymphocytic choriomeningitis virus (LCMV), itacitinib and fedratinib performed suboptimally. Ruxolitinib demonstrated excellent clinical efficacy in both HLH models. RNA-sequencing of splenocytes from LCMV-infected Prf1-/- mice revealed that itacitinib targeted inflammatory and metabolic pathway genes in CD8 T cells, while fedratinib targeted genes regulating cell proliferation and metabolism. In monocytes, neither drug conferred major transcriptional impacts. Consistent with its superior clinical effects, ruxolitinib exerted the greatest transcriptional changes in CD8 T cells and monocytes, targeting more genes across several biologic pathways, most notably JAK-dependent pro-inflammatory signaling. We conclude that JAK1 inhibition is sufficient to curtail CpG-induced disease, but combined inhibition of JAK1 and JAK2 is needed to best control LCMV-induced immunopathology.

Definitions of hospital-acquired pneumonia in trauma research: a systematic review.

PURPOSE: What are reported definitions of HAP in trauma patient research? METHODS: A systematic review was performed using the PubMed/MEDLINE database. We included all English, Dutch, and German original research papers in adult trauma patients reporting diagnostic criteria for hospital-acquired pneumonia diagnosis. The risk of bias was assessed using the MINORS criteria. RESULTS: Forty-six out of 5749 non-duplicate studies were included. Forty-seven unique criteria were reported and divided into five categories: clinical, laboratory, microbiological, radiologic, and miscellaneous. Eighteen studies used 33 unique guideline criteria; 28 studies used 36 unique non-guideline criteria. CONCLUSION: Clinical criteria for diagnosing HAP-both guideline and non-guideline-are widespread with no clear consensus, leading to restrictions in adequately comparing the available literature on HAP in trauma patients. Studies should at least report how a diagnosis was made, but preferably, they would use pre-defined guideline criteria for pneumonia diagnosis in a research setting. Ideally, one internationally accepted set of criteria is used to diagnose hospital-acquired pneumonia. LEVEL OF EVIDENCE: Level III.

Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.

Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline NBN variants and identified 25 unique, putatively damaging NBN coding variants in 50 patients. Compared with the frequency of NBN variants in gnomAD non-cancer controls (189 unique, putatively damaging NBN coding variants in 472 of 118,479 individuals) we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.8). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as non-functional or partially functional. Finally, we found that germline NBN variant carriers, all of which were identified as heterozygous genotypes, showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, and the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.

The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea.

OBJECTIVES: There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with vancomycin-resistant enterococci (VRE) because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). METHODS: This retrospective quasi-experimental study was conducted at a tertiary-care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the haematology unit before (phase 1) and after (phase 2) the policy change. RESULTS: At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval (CI): -0.053 to 0.023, P=0.45 and 0.000, 95% CI: -0.002 to 0.002, P=0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the haematology unit (-0.285, 95% CI: -0.618 to 0.048, P=0.09 and -0.018, 95% CI: -0.036 to 0.000, P = 0.054, respectively) did not change significantly across the two phases. CONCLUSIONS: Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the haematology unit. Horizontal intervention for multi-drug-resistant organisms, including measures such as enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

Insights into the Molecular Mechanisms of Genetic Predisposition to Hematopoietic Malignancies: The Importance of Gene-Environment Interactions.

SUMMARY: The recognition of host genetic factors underlying susceptibility to hematopoietic malignancies has increased greatly over the last decade. Historically, germline predisposition was thought to primarily affect the young. However, emerging data indicate that hematopoietic malignancies that develop in people of all ages across the human lifespan can derive from germline predisposing conditions and are not exclusively observed in younger individuals. The age at which hematopoietic malignancies manifest appears to correlate with distinct underlying biological pathways. Progression from having a deleterious germline variant to being diagnosed with overt malignancy involves complex, multistep gene-environment interactions with key external triggers, such as infection and inflammatory stimuli, driving clonal progression. Understanding the mechanisms by which predisposed clones transform under specific pressures may reveal strategies to better treat and even prevent hematopoietic malignancies from occurring.Recent unbiased genome-wide sequencing studies of children and adults with hematopoietic malignancies have revealed novel genes in which disease-causing variants are of germline origin. This paradigm shift is spearheaded by findings in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) as well as acute lymphoblastic leukemia, but it also encompasses other cancer types. Although not without challenges, the field of genetic cancer predisposition is advancing quickly, and a better understanding of the genetic basis of hematopoietic malignancies risk affects therapeutic decisions as well as genetic counseling and testing of at-risk family members.

Adult-onset cancer predisposition syndromes in children and adolescents - to test or not to test?

With the increasing use of comprehensive germline genetic testing of children and adolescents with cancer, it has become evident that pathogenic variants (PVs) in adult-onset cancer predisposition genes (aoCPGs) underlying adult-onset cancer predisposition syndromes (aoCPS) such as Lynch syndrome or hereditary breast and ovarian cancer are enriched and reported in one to two percent of children and adolescents with cancer. However, the causal relationship between PVs in aoCPGs and childhood cancer is still under investigation. The best studied examples include heterozygous PVs in mismatch repair genes associated with Lynch syndrome in children with mismatch repair deficient high-grade glioma, heterozygous PVs in BARD1 in childhood neuroblastoma, and heterozygous PVs in BRCA2 in children with rhabdomyosarcoma. The low penetrance for pediatric cancers is considered to result from a combination of the low baseline risk of cancer in childhood and the report of only a modest relative risk of disease in childhood. Therefore, we do not advise that healthy children empirically be tested for PVs in an aoCPG before adulthood outside a research study. However, germline panel testing is increasingly being performed in children and adolescents with cancer, and exome and genome sequencing may be offered more commonly in this population in the future. The precise pediatric cancer risks and spectra associated with PVs in aoCPGs, underlying cellular mechanisms and somatic mutational signatures, as well as treatment response, second neoplasm risks and psycho-oncological aspects require further research.

Towards the Magic Radioactive Bullet: Improving Targeted Radionuclide Therapy by Reducing the Renal Retention of Radioligands.

Targeted radionuclide therapy (TRT) is an emerging field and has the potential to become a major pillar in effective cancer treatment. Several pharmaceuticals are already in routine use for treating cancer, and there is still a high potential for new compounds for this application. But, a major issue for many radiolabeled low-to-moderate-molecular-weight molecules is their clearance via the kidneys and their subsequent reuptake. High renal accumulation of radioactive compounds may lead to nephrotoxicity, and therefore, the kidneys are often the dose-limiting organs in TRT with these radioligands. Over the years, different strategies have been developed aiming for reduced kidney retention and enhanced therapeutic efficacy of radioligands. In this review, we will give an overview of the efforts and achievements of the used strategies, with focus on the therapeutic potential of low-to-moderate-molecular-weight molecules. Among the strategies discussed here is coadministration of compounds that compete for binding to the endocytic receptors in the proximal tubuli. In addition, the influence of altering the molecular design of radiolabeled ligands on pharmacokinetics is discussed, which includes changes in their physicochemical properties and implementation of cleavable linkers or albumin-binding moieties. Furthermore, we discuss the influence of chelator and radionuclide choice on reabsorption of radioligands by the kidneys.

Blood biomarkers for the differentiation between central and peripheral vertigo in the emergency department: a systematic review and meta-analysis.

BACKGROUND/INTRODUCTION: In patients with acute vestibular syndrome (AVS), differentiating between stroke and nonstroke causes is challenging in the emergency department (ED). Correct diagnosis of vertigo etiology is essential for early optimum treatment and disposition. OBJECTIVES: The aim of this systematic review and meta-analysis was to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of peripheral from central causes of AVS. METHODS: A literature search was conducted for studies published until January 1, 2023, in PubMed, Ovid Medline, and EMBASE databases analyzing biomarkers for the differentiation between central and peripheral AVS. The Quality Assessment of Diagnostic Accuracy Studies questionnaire 2 was used for quality assessment. Pooled standardized mean difference and 95% confidence intervals were calculated if a biomarker was reported in two or more studies. Heterogeneity among included studies was investigated using the I2 metric. RESULTS: A total of 17 studies with 859 central and 4844 peripheral causes of acute dizziness or vertigo, and analysis of 61 biomarkers were included. The general laboratory markers creatinine, blood urea nitrogen, albumin, C-reactive protein, glucose, HbA1c, leukocyte counts, and neutrophil counts and the brain-derived biomarkers copeptin, S100 calcium-binding protein ß (S100ß), and neuron-specific enolase (NSE) significantly differentiated central from peripheral causes of AVS. CONCLUSIONS: This systematic review and meta-analysis highlights the potential of generalized inflammatory markers and brain-specific blood protein markers of NSE and S100ß as diagnostic biomarkers for central from peripheral differentiation in AVS. These results, as a complement to clinical characteristics, provide guidance for future large-scale diagnostic research, in this challenging ED patient population.

Genomes for Nurses: Understanding and Overcoming Barriers to Nurses Utilizing Genomics.

Background: Genomic testing is an increasingly important technology within pediatric oncology that aids in cancer diagnosis, provides prognostic information, identifies therapeutic targets, and reveals underlying cancer predisposition. However, nurses lack basic knowledge of genomics and have limited self-assurance in using genomic information in their daily practice. This single-institution project was carried out at an academic pediatric cancer hospital in the United States with the aim to explore the barriers to achieving genomics literacy for pediatric oncology nurses. Method: This project assessed barriers to genomic education and preferences for receiving genomics education among pediatric oncology nurses, nurse practitioners, and physician assistants. An electronic survey with demographic questions and 15 genetics-focused questions was developed. The final survey instrument consisted of nine sections and was pilot-tested prior to administration. Data were analyzed using a ranking strategy, and five focus groups were conducted to capture more-nuanced information. The focus group sessions lasted 40 min to 1 hour and were recorded and transcribed. Results: Over 50% of respondents were uncomfortable with or felt unprepared to answer questions from patients and/or family members about genomics. This unease ranked as the top barrier to using genomic information in clinical practice. Discussion: These results reveal that most nurses require additional education to facilitate an understanding of genomics. This project lays the foundation to guide the development of a pediatric cancer genomics curriculum, which will enable the incorporation of genomics into nursing practice.

The carbon footprint of different modes of birth in the UK and the Netherlands: An exploratory study using life cycle assessment.

OBJECTIVE: To compare the carbon footprint of caesarean and vaginal birth. DESIGN: Life cycle assessment (LCA). SETTING: Tertiary maternity units and home births in the UK and the Netherlands. POPULATION: Birthing women. METHODS: A cradle-to-grave LCA using openLCA software to model the carbon footprint of different modes of delivery in the UK and the Netherlands. MAIN OUTCOME MEASURES: 'Carbon footprint' (in kgCO2 equivalents [kgCO2 e]). RESULTS: Excluding analgesia, the carbon footprint of a caesarean birth in the UK was 31.21 kgCO2 e, compared with 12.47 kgCO2 e for vaginal birth in hospital and 7.63 kgCO2 e at home. In the Netherlands the carbon footprint of a caesarean was higher (32.96 kgCO2 e), but lower for vaginal birth in hospital and home (10.74 and 6.27 kgCO2 e, respectively). Emissions associated with analgesia for vaginal birth ranged from 0.08 kgCO2 e (with opioid analgesia) to 237.33 kgCO2 e (nitrous oxide with oxygen). Differences in analgesia use resulted in a lower average carbon footprint for vaginal birth in the Netherlands than the UK (11.64 versus 193.26 kgCO2 e). CONCLUSION: The carbon footprint of a caesarean is higher than for a vaginal birth if analgesia is excluded, but this is very sensitive to the analgesia used; use of nitrous oxide with oxygen multiplies the carbon footprint of vaginal birth 25-fold. Alternative methods of pain relief or nitrous oxide destruction systems would lead to a substantial improvement in carbon footprint. Although clinical need and maternal choice are paramount, protocols should consider the environmental impact of different choices.

Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation.

BACKGROUND: Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a). METHODS: Untargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The atherogenicity of the observed Lp(a)-associated lipids was tested ex vivo in primary human monocytes by RNA sequencing, ELISA, Western blot, and transendothelial migratory assays. Using immunofluorescence staining and single-cell RNA sequencing, the phenotype of macrophages was investigated in human atherosclerotic lesions. RESULTS: Compared with healthy individuals with low/normal Lp(a) levels (median, 7 mg/dL [18 nmol/L]; n=13), individuals with elevated Lp(a) levels (median, 87 mg/dL [218 nmol/L]; n=12) demonstrated an increase in lipid species, particularly diacylglycerols (DGs) and lysophosphatidic acid (LPA). DG and the LPA precursor lysophosphatidylcholine were enriched in the Lp(a) fraction. Ex vivo stimulation with DG(40:6) demonstrated a significant upregulation in proinflammatory pathways related to leukocyte migration, chemotaxis, NF-κB (nuclear factor kappa B) signaling, and cytokine production. Functional assessment showed a dose-dependent increase in the secretion of IL (interleukin)-6, IL-8, and IL-1ß after DG(40:6) and DG(38:4) stimulation, which was, in part, mediated via the NLRP3 (NOD [nucleotide-binding oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome. Conversely, LPA-stimulated monocytes did not exhibit an inflammatory phenotype. Furthermore, activation of monocytes by DGs and LPA increased their transendothelial migratory capacity. Human atherosclerotic plaques from patients with high Lp(a) levels demonstrated colocalization of Lp(a) with M1 macrophages, and an enrichment of CD68+IL-18+TLR4+ (toll-like receptor) TREM2+ (triggering receptor expressed on myeloid cells) resident macrophages and CD68+CASP1+ (caspase) IL-1B+SELL+ (selectin L) inflammatory macrophages compared with patients with low Lp(a). Finally, potent Lp(a)-lowering treatment (pelacarsen) resulted in a reduction in specific circulating DG lipid subspecies in patients with cardiovascular disease with elevated Lp(a) levels (median, 82 mg/dL [205 nmol/L]). CONCLUSIONS: Lp(a)-associated DGs and LPA have a potential role in Lp(a)-induced monocyte inflammation by increasing cytokine secretion and monocyte transendothelial migration. This DG-induced inflammation is, in part, NLRP3 inflammasome dependent.

Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti-PD-1 Monotherapy: A Report from the International RRD Consortium.

Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.7 years). After second progression/recurrence (n = 55), continuing ICI-based salvage prolonged survival to 11.6 months (n = 38; P < 0.001), particularly for those with extreme mutation burden (P = 0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and the immune microenvironment. Response to reirradiation was explained by an absence of deleterious postradiation indel signatures (ID8). CTLA4 expression increased over time, and subsequent CTLA4 inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to the reinvigoration of peripheral immune and radiologic responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide a mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology. SIGNIFICANCE: Hypermutant RRD-HGG are susceptible to checkpoint inhibitors beyond initial progression, leading to improved survival when reirradiation and synergistic immune/targeted agents are added. This is driven by their unique biological and immune properties, which evolve over time. Future research should focus on combinatorial regimens that increase patient survival while limiting immune toxicity. This article is featured in Selected Articles from This Issue, p. 201.

Environmental sustainability and gynaecological surgery: Which factors influence behaviour? An interview study.

OBJECTIVE: To assess the various factors that influence environmentally sustainable behaviour in gynaecological surgery and examine the differences between gynaecologists and residents. DESIGN: An interview study. SETTING: Academic and non-academic hospitals in the Netherlands. POPULATION: Gynaecologists (n = 10) and residents (n = 6). METHODS: Thematic analysis of semi-structured interviews to determine the various factors that influence environmentally sustainable behaviour in gynaecological surgery and to examine the differences between gynaecologists and residents. By using the Desmond framework and the COM-B BCW, both organisational and individual factors related to behaviour were considered. MAIN OUTCOME MEASURES: Factors that influence environmentally sustainable behaviour. RESULTS: Awareness is increasing but practical knowledge is insufficient. It is crucial to integrate education on the environmental impact of everyday decisions for residents and gynaecologists. Gynaecologists make their own choices but residents' autonomy is limited. There is the necessity to provide environmentally sustainable surgical equipment without compromising other standards. There is a need for a societal change that encourages safe and open communication about environmental sustainability. To transition to environmentally sustainable practices, leadership, time, collaboration with the industry and supportive regulatory changes are essential. CONCLUSION: This study lays the groundwork for promoting more environmentally sustainable behaviour in gynaecological surgery. The key recommendations, addressing hospital regulations, leadership, policy revisions, collaboration with the industry, guideline development and education, offer practical steps towards a more sustainable healthcare system. Encouraging environmentally sustainable practices should be embraced to enhance the well-being of both our planet and our population, driving us closer to a more environmentally sustainable future in healthcare.

Holo-analysis of the effects of xylo-oligosaccharides on broiler chicken performance.

1. Xylo-oligosaccharides (XOS) stimulate proliferation of beneficial bacteria in the gastrointestinal tract of broiler chickens. This results in enhanced utilisation of dietary non-starch polysaccharides and increased production of valuable short-chain fatty acids. However, these positive effects do not always translate into improved bird productive performance, with inconsistent performance responses observed between bird trials.2. A holo-analysis was conducted to determine the effects of supplementing XOS into broiler diets on bird feed intake, body weight gain, feed conversion and mortality. This was done by comparing the XOS supplemented treatment to the control treatment. A total of 53 studies which met the criteria for inclusion were used in the analysis.3. The results showed that XOS had a notable positive impact on bird mortality; XOS reduced mortality by 0.69% for every 1% increment in the control group. XOS supplementation induced a positive effect on the feed conversion ratio (FCR). However, the efficacy of XOS at improving FCR was dependent on the efficiency of the control group (performance of the flock), and the concentration of total arabinoxylan, protein and phytase in the diet. There were insufficient data points to predict the effect of XOS on body weight and feed intake.4. In conclusion, the holo-analysis revealed that supplementing XOS to broiler chicken diets reduces bird mortality. XOS can also improve FCR, but the scale of response is dependent on the diet composition and control flock performance. Additional studies are required to confirm the effects of XOS on body weight and feed intake.

Improved diagnostic performance of susceptibility-weighted imaging with compressed sensing-sensitivity encoding and neuromelanin-sensitive MRI for Parkinson's disease and atypical Parkinsonism.

AIM: To verify the diagnostic performance of the loss of nigrosome-1 on susceptibility-weighted imaging (SWI) with compressed sensing-sensitivity encoding (CS-SENSE) and neuromelanin on neuromelanin-sensitive (NM) magnetic resonance imaging (MRI) for the diagnosis of Parkinson's disease (PD) and atypical Parkinsonism. MATERIALS AND METHODS: A total of 195 patients who underwent MRI between October 2019 and February 2020, including SWI, with or without CS-SENSE, and NM-MRI, were reviewed retrospectively. Two neuroradiologists assessed the loss of nigrosome-1 on SWI and neuromelanin on the NM-MRI. The result of N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane positron-emission tomography (PET) was set as the reference standard. RESULTS: When CS-SENSE was applied for nigrosome-1 imaging on SWI, the non-diagnostic scan rate was lowered significantly from 19.3% (17/88) to 5.6% (6/107; p=0.004). Diagnosis of PD and atypical Parkinsonism based on the loss of nigrosome-1 on SWI and based on NM-MRI showed good diagnostic value (area under the curve [AUC] 0.821, 95% confidence interval [CI] = 0.755-0.875: AUC 0.832, 95% CI = 0.771-0.882, respectively) with a substantial inter-reader agreement (κ = 0.791 and 0.681, respectively). Combined SWI and neuromelanin had a similar discriminatory ability (AUC 0.830, 95% CI = 0.770-0.880). Similarly, the diagnosis of PD was excellent. CONCLUSIONS: CS-SENSE may add value to the diagnostic capability of nigrosome-1 on SWI to reduce the nondiagnostic scan rates. Furthermore, loss of nigrosome-1 on SWI or volume loss of neuromelanin on NM-MRI may be helpful for diagnosing PD.