Notes

Single-Neuron RNA Change Evaluation through Mass Spectrometry: Characterizing RNA Change Patterns and also Characteristics using Single-Cell Solution.
cepts, as well as the malleability of self-efficacy beliefs for long-term threats, are discussed. The use of repeated versus single interventions and different threat types (eg, health and social threats) should be tested empirically to establish a way forward for diversifying intervention approaches.

ClinicalTrials.gov NCT05321238; https//www.clinicaltrials.gov/ct2/show/NCT05321238.
ClinicalTrials.gov NCT05321238; https//www.clinicaltrials.gov/ct2/show/NCT05321238.Orthostatic hypotension (OH) is a well-recognized phenomenon occurring in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), and is associated with significant morbidity and mortality. A retrospective analysis of patients admitted for first ASCT between June 2012 and April 2014 found that 161/222 (73%) patients were diagnosed with OH during the course of ASCT, including 51 patients who were found to have OH on the day of first orthostatic vitals check. Excluding these 51 patients, 110/171 (64%) patients developed OH during the peri-transplant period, at a median of 7 days post ASCT (95% CI 6.5-8.5). OH did not significantly impact length of hospitalization, progression free and overall survival. Multivariable analysis revealed four risk factors (i.e. ≥0.5% weight loss/day, white race, gabapentin, antihypertensives) and two protective factors (i.e. antihistamine, proton pump inhibitor) associated with the development of peri-transplant OH.
Chronic pain is associated with an elevated risk of suicidal ideation (SI).

We aimed to examine if the presence or the search for Meaning in Life (MiL) are associated with less SI and explore whether MiL profiles emerge in our cohort. These profiles can be described as high presence-high search, high presence-low search, low presence-low search, and low presence-high search.

In this observational study, we recruited 70 patients who were referred to the Multidisciplinary Pain Center of the Geneva University Hospitals and who answered positively to question 9 on the Beck Depression Inventory, 2nd Edition, investigating SI. Patients who agreed to participate in the study were further investigated; they participated in a structured diagnostic interview to screen for psychiatric diagnoses. During this interview, they completed the Meaning in Life Questionnaire and the semistructured Scale for Suicide Ideation (SSI) to assess the characteristics and severity of SI.

There was a statistically significant corrchotherapeutic interventions for chronic pain patients in order to reduce the suicidal risk and more accurately determine patients' suffering.
The COVID-19 pandemic has caused changes in technology use worldwide, both socially and economically. This pandemic crisis has brought additional measures such as contact-tracing apps (CTAs) to help fight against spread of the virus. Unfortunately, the low adoption rate of these apps affected their success. There could be many reasons for the low adoption, including concerns of security and privacy, along with reported issues of trust in CTAs. Some concerns are related with how CTAs could be used as surveillance tools or their potential threats to privacy as they involve health data. For example, in Estonia, the CTA named HOIA had approximately 250,000 downloads in the middle of January 2021. However, in 2021, only 4.7% of the population used HOIA as a COVID-19 CTA. The reasons for the low adoption include lack of competency, and privacy and security concerns. This lower adoption and the lack of trustworthiness persist despite efforts of the European Union in building ethics and trustworthy artificial intel of this work is limited to HOIA and health apps that use similar contact-tracing methods. However, the findings can contribute to gaining a broader understanding and awareness of the need for designing trustworthy technologies. Moreover, this work can help to provide design recommendations that ensure trustworthiness in CTAs, and the ability of AI to use highly sensitive data and serve society.
Osilodrostat is a new 11β-hydroxylase inhibitor with a mode of action analogous to Metyrapone. The objective of this study was to compare steroidogenic profiles in patients treated with either Osilodrostat or Metyrapone for adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome (CS).

Patients followed up at Cochin hospital Endocrinology department between March 2019 and December 2021 for an ACTH-dependent CS, controlled by either Osilodrostat or Metyrapone, were included. A serum profile of five steroids (cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione and testosterone) was determined using UPLC- tandem mass spectrometry (UPLC-MS/MS).

Nineteen patients treated with Osilodrostat, eight patients treated with Metyrapone and six patients treated with consecutive Metyrapone then Osilodrostat were included. Hypocortisolism (basal cortisol <100 nmol/L) was found in 48% of patients treated with Osilodrostat and 7% of patients treated with Metyrapone. 11-deoxycortisol and androstrs in routine care suggests that Osilodrostat has a less specific effect on the inhibition of steroidogenic enzymes than Metyrapone. This might explain a smaller increase in 11-deoxycortisol and androgen levels in patients treated with Osilodrostat.Compared to Asian and Latin American populations, sinonasal NK- or T-cell lymphoma is rare in Europe. All patients with sinonasal NK- or T-cell lymphoma in Denmark from 1980 to 2017 were validated histologically, and the disease behavior and demographics were extracted from medical records and national registries. Prognostic factors associated with mortality were determined using survival statistics. We included 56 patients 40 extranodal NK/T-cell lymphoma (nasal type) (ENKTCL) and 16 peripheral T-cell lymphoma (not otherwise specified) (PTCL). The median age was 66, and most patients were male (72%). The ENKTCL and PTCL 5-year overall survival was 48% and 50%, respectively; progression-free survival was 38% for both. With ENKTCL, stage and performance status increased mortality significantly (HR = 8.6;  = 0.04). In conclusion, disseminated disease had a dismal outcome and the onset of ENKTCL in this ethnically homogeneous European cohort was about a decade later than reported in Asian populations.The untangling or overwinding of genetic material is an inevitable part of DNA replication, repair, recombination, and transcription. Topoisomerases belong to a conserved enzyme family that amends DNA topology during various processes of DNA metabolism. To relax the genetic material, topoisomerases transiently break the phosphodiester bond on one or both DNA strands and remain associated with the cleavage site by forming a covalent enzyme-DNA intermediate. This releases torsional stress and allows the broken DNA to be re-ligated by the enzyme. The biological function of topoisomerases ranges from the separation of sister chromatids following DNA replication to the aiding of chromosome condensation and segregation during mitosis. Topoisomerases are also actively involved in meiotic recombination. The unicellular apicomplexan parasite, Plasmodium falciparum, harbors different topoisomerase subtypes, some of which have substantially different sequences and functions from their human counterparts. This review highlights the biological function of each identified Plasmodium topoisomerase along with a comparative analysis of their orthologs in human or other model organisms. There is also a focus on recent advancements towards the development of topoisomerase chemical inhibitors, underscoring the druggability of unique topoisomerase subunits that are absent in humans. Plasmodium harbors three distinct genomes in the nucleus, apicoplast, and mitochondria, respectively, and undergoes non-canonical cell division during the schizont stage of development. This review emphasizes the specific developmental stages of Plasmodium on which future topoisomerase research should focus.Pharmacokinetics of cyclophosphamide has been explored to optimize conditioning dosing. We hypothesized that post-transplant cyclophosphamide (PTCy) metabolite carboxy-ethyl phosphoramide mustard (CEPM) pharmacokinetics might impact haploidentical transplantation (haplo-HCT) outcomes. CEPM area under the curve (AUC.PEG-asparaginase is a key component in treatment regimens for acute lymphoblastic leukemia (ALL). Major side effects include thrombosis and bleeding; however, there is currently no consensus on methods to prevent these complications. In this multi-center retrospective cohort study of 101 adults, we compared two prophylaxis strategies cryoprecipitate and fresh frozen plasma (Cryo/FFP) versus cryoprecipitate and antithrombin (ATIII). The overall incidence of venous thromboembolism (VTE) was not significantly different between the two groups (19.7% for Cryo/FFP and 8.6% in Cryo/ATIII,  = 0.18). Given the significant cost associated with ATIII without a clear benefit, a careful benefit and risk analysis should be considered before utilizing ATIII as a prophylaxis strategy to prevent thrombosis or bleeding following asparaginase administration.
The
gene has recently garnered attention as a likely cause of arrhythmogenic cardiomyopathy, which is considered an actionable genetic condition. However, the association with disease in an unselected clinical population is unknown. We hypothesized that individuals with loss-of-function variants in
(

) would have increased odds for arrhythmogenic cardiomyopathy-associated phenotypes versus variant-negative controls in the Geisinger MyCode cohort.

We identified rare, putative

among 171 948 individuals with exome sequencing linked to health records. Associations with arrhythmogenic cardiomyopathy phenotypes from available diagnoses and cardiac evaluations were investigated.

Sixty individuals (0.03%; median age 58 years [47-70 interquartile range], 43% male) harbored 27 unique

. These individuals had significantly increased odds ratios for dilated cardiomyopathy (odds ratio, 4.9 [95% CI, 2.6-7.6];
<0.001), supraventricular tachycardia (odds ratio, 3.2 [95% CI, 1.1-5.6];
=0.048), and left-dominant arrhythmogenic cardiomyopathy (odds ratio, 4.2 [95% CI, 1.4-7.9];
=0.03). Echocardiography revealed reduced left ventricular ejection fraction (52±13% versus 57±9%;
=0.001) associated with

. find more Overall, at least 9% of

patients demonstrated evidence of penetrant disease.


variants are associated with increased odds of ventricular arrhythmia and dysfunction in an unselected clinical population. These findings support genomic screening of
for actionable secondary findings.
FLNCLOF variants are associated with increased odds of ventricular arrhythmia and dysfunction in an unselected clinical population. These findings support genomic screening of FLNC for actionable secondary findings.Quantitative and qualitative measurements of trace-level analytes in plants or foodstuffs, e.g., secondary metabolites like carotenoids, are often performed at centralized core facilities or off-site laboratories. However, preparation, storage, and/or transport of both intact samples and sample extracts may be cumbersome and complicated, especially for air-sensitive analytes. We describe the development of inexpensive swellable microextraction (SweME) devices for extraction and storage of nonpolar analytes. SweME devices consist of a thin layer of poly(dimethylsiloxane) (PDMS) grafted onto a stainless steel support. Pretreating the SweME device with small volumes of the organic solvent causes the PDMS to swell. The swollen SweME device can then be immersed directly into complex matrices for absorptive extraction of low-molecular-weight, nonpolar analytes. Following storage, analytes can be solvent-desorbed prior to characterization. Proof-of-principle work with carotenoids from tomatoes and carrots demonstrates that SweME is appropriate for semiquantitative analyses and increases the stability of air-sensitive analytes during storage at ambient temperatures as compared to the solvent extracts.
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