bluuebunny/crossref_metadata_2025_split huggingface dataset:
A preliminary framework for managing sleep inertia in occupational settings
Authors: Kovac Katya , Vincent Grace E , Paterson Jessica L , Hilditch Cassie J , Ferguson Sally A 
Published: November 2023

Abstract
Sleep inertia, the temporary period of impairment experienced upon waking, is a safety hazard that has been implicated in serious work-related incidents resulting in injuries as well as the loss of life and assets. As such, sleep inertia warrants formal management in industries where personnel are required to undertake their role soon after waking (e.g. emergency services, engineers, and health care). At present, there is a lack of practical, evidence-based guidance on how sleep inertia could be formally managed at an organizational level. We propose a preliminary framework for managing sleep inertia based on the translation of research findings into specific work procedure modifications/control mechanisms. Within the framework, work procedure modifications/control mechanisms to manage sleep inertia are organized into three levels: (1) modifications/controls that eliminate the chance of sleep inertia, (2) modifications/controls that reduce sleep inertia severity, and (3) modifications/controls that manage the risk of errors during sleep inertia. Practical considerations, limitations, and areas of further research are highlighted for each modification/control to help determine how readily each control measure could be implemented by industries at present. A guide for organizations to use this preliminary framework of sleep inertia management is put forward, as well as the next research priorities to strengthen the utility and evidence base of the framework.
This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection.
Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis
Authors: Narasimman Manasa , Hernaez Ruben , Cerda Vanessa , Lee MinJae , Sood Anubha , Yekkaluri Sruthi , Khan Aisha , Quirk Lisa , Liu Yan , Kramer Jennifer R. , Craddock Lee Simon , Murphy Caitlin C. , Tiro Jasmin A. , Singal Amit G. 
Published: November 2023

Background and Aims:
The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms.

Approach and Results:
We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance.

Conclusions:
Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.
Effects of rurality on distance and time traveled to receive vaccination against Mpox — New Mexico and Idaho 2022–2023
Authors: Stadelman-Behar Anna M. , Cahill Megan E. , Newell Katherine , Sievers Marla , Gehre Mika , Carter Kris K. , Sosin Daniel M. , Torrone Elizabeth A. 
Published: November 2023

ABSTRACT
We compared mpox vaccination access between urban and rural residents who received ≥1 JYNNEOS dose using immunization data in Idaho and New Mexico. Rural residents traveled five times farther and three times longer than urban residents to receive mpox vaccination. Increasing mpox vaccine availability to healthcare facilities might increase uptake.
Facility HIV Self-Testing in Outpatient Departments: An Assessment of Characteristics and Concerns of Outpatients Who Opt Out of Testing in Malawi
Authors: Shaba Frackson , Balakasi Kelvin T. , Offorjebe Ogechukwu A. , Nyirenda Mike , Wong Vincent J. , Gupta Sundeep K. , Hoffman Risa M. , Dovel Kathryn 
Published: November 2023

Background:
Facility HIV self-testing (HIVST) in outpatient departments can dramatically increase testing among adult outpatients. However, it is still unclear why populations opt out of facility HIVST and reasons for opt outing. Using data from a parent facility HIVST trial, we sought to understand individual characteristics associated with opting out of facility HIVST and reported reasons for not testing.

Methods:
Exit surveys were conducted with outpatients aged ≥15 years at 5 facilities in Central and Southern Malawi randomized to the facility HIVST arm of the parent trial. Outpatients were eligible for our substudy if they were offered HIVST and eligible for HIV testing (ie, never previously tested HIV positive and tested ≥12 months ago or never tested). Summary statistics and multivariate regression models were used.

Results:
Seven hundred seventy-one outpatients were included in the substudy. Two hundred sixty-three (34%) opted out of HIVST. Urban residency (adjusted risk ratios [aRR] 3.48; 95% CI: 1.56 to 7.76) and self-reported poor health (aRR 1.86; 95% CI: 1.27 to 2.72) were associated with an increased risk of opting out. Male participants had a 69% higher risk of opting out (aRR 1.69; 95% CI: 1.14 to 2.51), with risk being 38% lower among working male participants. Primary reasons for not testing were feeling unprepared to test (49·4%) and perceived low risk of HIV infection (30·4%)—only 2.6% believed that HIVST instructions were unclear, and 1.7% were concerned about privacy.

Conclusion:
Working, risky sexual behavior, rural residence, and good self-rated health were positively associated with opting out of HIVST among outpatients. Strategies to address internalized barriers, such as preparedness to test and perceived need to test, should be incorporated into facility HIVST interventions.
Brief Report: Incidence and Management of Complex Kidney Situations Among On-Demand and Daily HIV Pre-Exposure Prophylaxis Users
Authors: Liegeon Geoffroy , Brun Alexandre , Hamet Gwenn , Zeggagh Jeremy , Pintado Claire , Loze Bénédicte , Ponscarme Diane , Rozenbaum Willy , Molina Jean-Michel 
Published: November 2023

Background:
We evaluated complex pre-exposure prophylaxis (PrEP) situations linked to kidney issues in a cohort of on-demand and daily PrEP users.

Setting:
We conducted a single-center retrospective cohort study in France including all PrEP users who received a tenofovir disoproxil (TD)—emtricitabine (FTC) prescription between January 1, 2012 and December 31, 2019 with at least 1 creatinine measurement available before and after PrEP initiation.

Methods:
A complex kidney situation (CKS) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m2 on 2 consecutive measurements. We estimated the incidence of this event, described case management, and identified associated factors using a Cox model.

Results:
Three thousand one hundred and fourteen individuals were included in this study. Almost all were men (99%) with a median age of 35 years, 25% had an eGFR <90 mL/minute/1.73m2 at baseline, and 65% used on-demand PrEP. Nine users (0.29%) had a CKS at baseline; 8/9 initiated on-demand PrEP without renal function worsening after a median (interquartile range [IQR]) follow-up time of 14 months (7–31). Thirteen cases of CKS occurred during the follow-up for a 0.25 per 100 person-years incidence (95% confidence interval [CI]: [0.14; 0.45]). On-demand PrEP was used in 7/13 participants with no further episode of confirmed eGFR <60 mL/minute/1.73m2 after a 17-month median follow-up (IQR 4–18). CKS was associated with an age ≥50 years (hazard ratio [HR] 13, 95% CI: [4–39]) or with a baseline eGFR <90 mL/minute/1.73m2 (HR 34, 95% CI: [4–261]). 9/22 CKS were linked to high-protein intake for weight training.

Conclusions:
CKS were rare in our cohort. On-demand PrEP did not result in subsequent renal function worsening in these few situations.
The Association of HIV Control and Immunosuppression With Risk of Non–AIDS-Defining Cancer Risk Among Patients on Antiretroviral Therapy
Authors: Dickey Brittney L. , Yanik Elizabeth L. , Thompson Zachary , Burkholder Greer , Kitahata Mari M. , Moore Richard D. , Jacobson Jeff , Mathews W. Christopher , Christopoulos Katerina A. , Fleming Julia , Napravnik Sonia , Achenbach Chad , Coghill Anna E. 
Published: November 2023

Background:
People living with HIV (PWH) are experiencing an increased prevalence of non–AIDS-defining cancers (NADCs). Our study investigated the association of immunosuppression and HIV control with NADCs among PWH on antiretroviral therapy (ART) in the United States.

Methods:
Among patients across 8 clinical cohorts on ART between 1996 and 2016, we assessed immune function and HIV control using 3 parameterizations of CD4 count and HIV-RNA viral load (VL): (1) CD4 or VL at ART initiation; (2) change in CD4 or VL after ART initiation; and (3) proportion of follow-up time at CD4 >500 cells/µL or VL <50 copies/mL. Cox models were used to ascertain the association of these measures with risk of a viral NADC or nonviral NADC.

Results:
Among 29,568 patients on ART, there were 410 nonviral NADCs and 213 viral NADCs. PWH with a CD4 <200 cells/µL at ART initiation had an 80% elevated risk for developing a viral NADC. Each increase of 100 cells/µL in CD4 after ART initiation decreased risk by 14%. For viral and nonviral NADCs, 10% more follow-up time spent with a CD4 >500 cells/µL was associated with decreased risk [viral, adjusted hazard ratio (aHR): 0.82; 95% confidence intervals (CI): 0.78 to 0.86; nonviral, aHR: 0.88; 95% CI: 0.86 to 91], even after accounting for CD4 at ART initiation. When examining HIV control only, 10% more time with VL <50 copies/mL was significantly associated with decreased viral (aHR: 0.85; 95% CI: 0.82 to 0.89) and nonviral NADC risk (aHR: 0.88; 95% CI: 0.85 to 0.90).

Conclusions:
This study demonstrates that even for PWH on ART therapy, maintaining HIV control is associated with lower risk of both viral and nonviral NADCs.
HIV Viral Load Patterns and Risk Factors Among Women in Prevention of Mother-To-Child Transmission Programs to Inform Differentiated Service Delivery
Authors: Jiang Wenwen , Ronen Keshet , Osborn Lusi , Drake Alison L. , Unger Jennifer A. , Matemo Daniel , Richardson Barbra A. , Kinuthia John , John-Stewart Grace 
Published: November 2023

Background:
Differentiated service delivery (DSD) approaches decrease frequency of clinic visits for individuals who are stable on antiretroviral therapy. It is unclear how to optimize DSD models for postpartum women living with HIV (PWLH). We evaluated longitudinal HIV viral load (VL) and cofactors, and modelled DSD eligibility with virologic failure (VF) among PWLH in prevention of mother-to-child transmission programs.

Methods:
This analysis used programmatic data from participants in the Mobile WAChX trial (NCT02400671). Women were assessed for DSD eligibility using the World Health Organization criteria among general people living with HIV (receiving antiretroviral therapy for ≥6 months and having at least 1 suppressed VL [<1000 copies/mL] within the past 6 months). Longitudinal VL patterns were summarized using group-based trajectory modelling. VF was defined as having a subsequent VL ≥1000 copies/mL after being assessed as DSD-eligible. Predictors of VF were determined using log-binomial models among DSD-eligible PWLH.

Results:
Among 761 women with 3359 VL results (median 5 VL per woman), a 3-trajectory model optimally summarized longitudinal VL, with most (80.8%) women having sustained low probability of unsuppressed VL. Among women who met DSD criteria at 6 months postpartum, most (83.8%) maintained viral suppression until 24 months. Residence in Western Kenya, depression, reported interpersonal abuse, unintended pregnancy, nevirapine-based antiretroviral therapy, low-level viremia (VL 200–1000 copies/mL), and drug resistance were associated with VF among DSD-eligible PWLH.

Conclusions:
Most postpartum women maintained viral suppression from early postpartum to 24 months and may be suitable for DSD referral. Women with depression, drug resistance, and detectable VL need enhanced services.
Factors Associated With Mortality in Patients With Immune-Mediated Rheumatic Diseases and COVID-19 From Latin America
Authors: Isnardi Carolina Ayelen , Alpizar-Rodriguez Deshire , Calderaro Débora Cerqueira , Marques Claudia Diniz Lopes , Pons-Estel Guillermo Javier , Xavier Ricardo Machado , Saurit Verónica , Pisoni Cecilia Nora , Tissera Yohana Soledad , D'Angelo Exeni Maria Eugenia , Alba Paula , Pereira Dora , Gobbi Carla Andrea , Gamba Maria Julieta , Alfaro María Agustina , Virasoro Belén María , Colunga-Pedraza Iris Jazmín , Irazoque-Palazuelos Fedra , Reyes-Cordero Greta , Rodriguez-Reyna Tatiana S. , Veloz-Aranda Jose Antonio , Skinner-Taylor Cassandra Michele , Juárez-Mora Ingrid Maribel , Silveira Luis H. , Pacheco Tena Cesar Francisco , Xibille-Friedmann Daniel Xavier , Ferreira Gilda Aparecida , Kakehasi Adriana Maria , Pinheiro Marcelo Medeiros , Gomides Ana Paula Monteiro , Pileggi Gecilmara Cristina Salviato , da Mota Licia Maria Henrique , dos Reis-Neto Edgard Torres , Ribeiro Sandra Lúcia Euzébio , de Azevedo Valadares Lilian David , Martínez-Martínez Marco Ulises 
Published: November 2023

Objective
To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population.

Methods
Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded.

Results
A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6–12.4), male sex (OR, 1.5; 95% CI, 1.1–2.1), living in Mexico (OR, 3.0; 95% CI, 2.0–4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0–2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3–2.4), and other diseases (OR, 2.6; 95% CI, 1.6–4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5–7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4–2.5) or rituximab (OR, 4.2; 95% CI, 2.7–6.6) were associated with mortality.

Conclusions
Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.
The Endothelium Modulates the Prothrombotic Phenotype of Factor V Leiden: Evidence from an Ex Vivo Model
Authors: Schwarz Nadine , Müller Jens , McRae Hannah L. , Reda Sara , Pezeshkpoor Behnaz , Oldenburg Johannes , Pötzsch Bernd , Rühl Heiko 
Published: November 2023

ABSTRACTBackgroundClinical expressivity of the thrombophilic factor V Leiden (FVL) mutation is highly variable. Increased activated protein C (APC) formation in response to thrombin formation has been observed in asymptomatic FVL carriers in vivo. Here we further explored this association using a recently developed endothelial colony forming cell (ECFC)-based ex-vivo model.MethodsECFCs and citrated plasma were obtained from FVL carriers with/without previous venous thromboembolism (VTE+/-, n=7 each) and seven healthy controls. Coagulation was activated by tissue factor in defibrinated recalcified plasma added to confluent cell cultures. Thrombin and APC concentration were measured over time and the respective areas under the curve (AUC) calculated. Additionally, inhibition kinetics of exogenously added APC and APC sensitivity of the prothrombinase complex were measured in plasma. Expression of thrombomodulin and endothelial protein C receptor (EPCR) on ECFCs was assessed using cell-based enzyme-linked immunosorbent assays.ResultsIn autologous plasma on ECFCs, the APC response to thrombin formation (AUC APC/AUC thrombin), was higher in FVL VTE-than FVL VTE+ patients (0.138 versus 0.028,P=0.026). APC inactivation kinetics, APC sensitivity, and thrombomodulin/EPCR expression on ECFCs did not differ between these cohorts and compared to healthy controls. Cross-over experiments with plasma from FVL VTE- and FVL VTE+ patients on non-FVL ECFCs yielded indistinguishable results. In contrast, in normal plasma on FVL VTE-ECFCs the APC response remained significantly higher than on FVL VTE+ ECFCs (0.052 versus 0.022,P=0.011).ConclusionsConsistent with results from previous in vivo experiments, APC response rates to thrombin formation were higher in asymptomatic FVL carriers compared to those with previous VTE. Our observations suggest that this increased APC response is driven by the endothelium. Further studies are warranted to elucidate yet unknown endothelial mechanisms that might modulate the clinical expressivity of FVL.
Engineered odorant receptors illuminate structural principles of odor discrimination
Authors: de March Claire A. , Ma Ning , Billesbølle Christian B. , Tewari Jeevan , del Torrent Claudia Llinas , van der Velden Wijnand J. C. , Ojiro Ichie , Takayama Ikumi , Faust Bryan , Li Linus , Vaidehi Nagarajan , Manglik Aashish , Matsunami Hiroaki 
Published: November 2023

AbstractA central challenge in olfaction is understanding how the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations. Vertebrate animals perceive odors via G protein-coupled odorant receptors (ORs). In humans, ∼400 ORs enable the sense of smell. The OR family is composed of two major classes: Class I ORs are tuned to carboxylic acids while Class II ORs, representing the vast majority of the human repertoire, respond to a wide variety of odorants. How ORs recognize chemically diverse odorants remains poorly understood. A fundamental bottleneck is the inability to visualize odorant binding to ORs. Here, we uncover fundamental molecular properties of odorant-OR interactions by employing engineered ORs crafted using a consensus protein design strategy. Because such consensus ORs (consORs) are derived from the 17 major subfamilies of human ORs, they provide a template for modeling individual native ORs with high sequence and structural homology. The biochemical tractability of consORs enabled four cryoEM structures of distinct consORs with unique ligand recognition properties. The structure of a Class I consOR, consOR51, showed high structural similarity to the native human receptor OR51E2 and yielded a homology model of a related member of the human OR51 family with high predictive power. Structures of three Class II consORs revealed distinct modes of odorant-binding and activation mechanisms between Class I and Class II ORs. Thus, the structures of consORs lay the groundwork for understanding molecular recognition of odorants by the OR superfamily.
A liquid-to-solid phase transition of biomolecular condensates drivesin vivoformation of yeast amyloids and prions
Authors: Alieva Maya K. , Nikishina Sophia B. , Kireev Igor I. , Golyshev Sergei A. , Tyurin-Kuzmin Pyotr A. , Ivanova Liudmila V. , Alexandrov Alexander I. , Kushnirov Vitaly V. , Dergalev Alexander A. 
Published: November 2023

AbstractLiquid-liquid phase separation (LLPS) and liquid-solid phase transition (LSPT) of amyloidogenic proteins are now being intensively studied as a potentially widespread mechanism of pathological amyloids formation. However, the possibility and importance of such a mechanism in living systems is still questionable. Here, we investigated the possibility of such LSPT for a series of yeast prion proteins-based constructs overproduced in yeast cells lacking any pre-existing amyloid template. By combining fluorescence and electron microscopy with biochemical and genetic approaches, we have shown that three such constructs (containing the prion domains (PDs) of either Sup35, Rnq1 or Mot3 proteins) form amyloid fibrils via the intermediate stage of liquid-like condensates, that age over time into the more solid-like hydrogels and amyloid bodies. In turn, LSPT of these constructs triggers prion conversion of the corresponding wild-type protein. Two other constructs studied (Ure2- and Sap30-based) are unable to phase separate in vivo and their amyloidogenesis is therefore strongly suppressed. Using PrK-resistant amyloid core mapping, we showed that Sup35PD amyloids formed via LSPT have a different molecular architecture compared to those formed via amyloid cross-seeding. Finally, we showed that physiological LLPS of wild-type Sup35 protein can increase its prion conversion in yeast.
DFNA5-mediated pyroptosis is a driver for venetoclax and azacytidine synergy in myeloid leukemia
Authors: Mahesh Aarthi Nivasini , Xin-Yi Joanne Lai , Jia Lin Mandy Tng , Lin Weilin , Wan Jia Cheng , Yoon Junho , Chen Kaiwen , Bhatt Shruti 
Published: November 2023

AbstractAcute myeloid leukemia (AML) remains the deadliest adult leukemia with dismal clinical outcomes. Since 2020, a combination of BCL-2 inhibitor (venetoclax, VEN) with hypomethylating agent (azacytidine/decitabine, AZA/DAC) has become a new standard of care in elderly or unfit AML patients. However, the underlying mechanism of synergy between venetoclax and azacytidine combination is not well understood. While apoptosis is regarded as the primary mode of cell death mechanism caused by the venetoclax and azacytidine combination, we provide novel evidence for pyroptosis as additional cell death mechanisms in response to venetoclax and azacytidine combination therapy. We found that long-term treatment with azacytidine caused hypomethylation and significant upregulation in DFNA5/GSDME, pore forming Gasdermin family gene that is otherwise silent in myeloid leukemia. We found that azacytidine mediates N-terminal pore-forming DFNA5 cleavage, membrane rupture, and subsequent pyroptosis ofDFNA5overexpressing cells in response to venetoclax and azacytidine. Deletion ofDFNA5reduced total cell viability, whereDFNA5KO cells exclusively underwent apoptosis while DFNA5 OE cells showed increased propidium iodide uptake, a marker for membrane rupture. Overall, our study establishesDFNA5as an important mediator of venetoclax and azacytidine-induced cell death via non-apoptotic mechanisms.