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Abstract Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood. Here we show that human WRNIP1 interacts with G4 structures and provide evidence for its contribution to G4 processing. The absence of WRNIP1 results in elevated levels of G4 structures, DNA damage and chromosome aberrations following treatment with PhenDC3, a G4-stabilizing ligand. Additionally, we establish a functional and physical relationship between WRNIP1 and the PIF1 helicase in G4 processing. In summary, our results suggest that WRNIP1 aids genome replication and maintenance by regulating G4 processing and this activity relies on Pif1 DNA helicase.

Abstract A simple and cheap way to recognize cervical cancer is using light microscopic analysis of Pap smear images. Training artificial intelligence-based systems becomes possible in this domain, e.g., to follow the European recommendation to screen negative smears to reduce false negative cases. The first step for such a process is segmenting the cells. A large and manually segmented dataset is required for this task, which can be used to train deep learning-based solutions. We describe a corresponding dataset with accurate manual segmentations for the enclosed cells. Altogether, the APACS23 (Annotated PAp smear images for Cell Segmentation 2023) dataset contains about 37 000 manually segmented cells and is separated into dedicated training and test parts, which could be used for an official benchmark of scientific investigations or a grand challenge.

Mircea Gabriel Stoleriu,1,2,&ast; Michael Pienn,3,4,&ast; Rudolf A Joerres,5 Peter Alter,6 Tamas Fero,7 Martin Urschler,8 Gabor Kovacs,3,9 Horst Olschewski,3,9 Hans-Ulrich Kauczor,7,10 Mark Wielpütz,7,10 Bertram Jobst,7,10 Tobias Welte,11 Jürgen Behr,2,12 Franziska C Trudzinski,10,13 Robert Bals,14,15 Henrik Watz,16 Claus F Vogelmeier,6 Jürgen Biederer,10,17,18,&ast; Kathrin Kahnert2,12,19,&ast; On behalf of the COSYCONET Study Group1Division for Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Medical Center; Munich-Gauting, Gauting, 82131, Germany; 2Institute for Lung Health and Immunity and Comprehensive Pneumology Center with the CPC-M bioArchive; Helmholtz Center Munich; Member of the German Lung Research Center (DZL), Munich, 81377, Germany; 3Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; 4Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; 5Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Hospital of Ludwig-Maximilians-University Munich (LMU), Munich, 80336, Germany; 6Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg (UMR), Member of the German Center for Lung Research (DZL), Marburg, 35033, Germany; 7Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany; 8Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria; 9University Clinic for Internal Medicine, Medical University of Graz, Division of Pulmonology, Graz, Austria; 10Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research DZL, Heidelberg, Germany; 11Department of Respiratory Medicine and Infectious Disease, Member of the German Center of Lung Research, Hannover School of Medicine, Hannover, Germany; 12Department of Medicine V, LMU University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany; 13Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany; 14Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, 66421, Germany; 15Helmholtz Institute for Pharmaceutical Research, Saarbrücken, 66123, Germany; 16Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Centre North, German Centre for Lung Research, Großhansdorf, Germany; 17Faculty of Medicine, Christian-Albrechts-Universität Zu Kiel, Kiel, Germany; 18University of Latvia, Faculty of Medicine, Riga, LV-1586, Latvia; 19MediCenterGermering, Germering, Germany&ast;These authors contributed equally to this workCorrespondence: Mircea Gabriel Stoleriu, Division of Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Marchioninistr. 15, 81377 Munich and Robert-Koch-Allee 2, Gauting, 82131, Germany, Tel +49 89 85791 4201, Email gabriel.stoleriu@helmholtz-munich.dePurpose: The aim of this study was to evaluate the association between computed tomography (CT) quantitative pulmonary vessel morphology and lung function, disease severity, and mortality risk in patients with chronic obstructive pulmonary disease (COPD).Patients and Methods: Participants of the prospective nationwide COSYCONET cohort study with paired inspiratory-expiratory CT were included. Fully automatic software, developed in-house, segmented arterial and venous pulmonary vessels and quantified volume and tortuosity on inspiratory and expiratory scans. The association between vessel volume normalised to lung volume and tortuosity versus lung function (forced expiratory volume in 1 sec [FEV1]), air trapping (residual volume to total lung capacity ratio [RV/TLC]), transfer factor for carbon monoxide (TLCO), disease severity in terms of Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D, and mortality were analysed by linear, logistic or Cox proportional hazard regression.Results: Complete data were available from 138 patients (39% female, mean age 65 years). FEV1, RV/TLC and TLCO, all as % predicted, were significantly (p < 0.05 each) associated with expiratory vessel characteristics, predominantly venous volume and arterial tortuosity. Associations with inspiratory vessel characteristics were absent or negligible. The patterns were similar for relationships between GOLD D and mortality with vessel characteristics. Expiratory venous volume was an independent predictor of mortality, in addition to FEV1.Conclusion: By using automated software in patients with COPD, clinically relevant information on pulmonary vasculature can be extracted from expiratory CT scans (although not inspiratory scans); in particular, expiratory pulmonary venous volume predicted mortality.Trial Registration: NCT01245933.Keywords: COPD, computed tomography, pulmonary vasculature, vessel volume, vessel tortuosity, lung function

Abstract Background Rotator cuff disorders, whether symptomatic or asymptomatic, may result in abnormal shoulder kinematics (scapular rotation and glenohumeral translation). This study aimed to investigate the effect of rotator cuff tears on in vivo shoulder kinematics during a 30° loaded abduction test using single-plane fluoroscopy. Materials and methods In total, 25 younger controls, 25 older controls and 25 patients with unilateral symptomatic rotator cuff tears participated in this study. Both shoulders of each participant were analysed and grouped on the basis of magnetic resonance imaging into healthy, rotator cuff tendinopathy, asymptomatic and symptomatic rotator cuff tears. All participants performed a bilateral 30° arm abduction and adduction movement in the scapular plane with handheld weights (0, 2 and 4 kg) during fluoroscopy acquisition. The range of upward–downward scapular rotation and superior–inferior glenohumeral translation were measured and analysed during abduction and adduction using a linear mixed model (loads, shoulder types) with random effects (shoulder ID). Results Scapular rotation was greater in shoulders with rotator cuff tendinopathy and asymptomatic rotator cuff tears than in healthy shoulders. Additional load increased upward during abduction and downward during adduction scapular rotation (P

Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin αvβ6 are emerging as powerful tools to overcome these challenges. The development of an integrin αvβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the αvβ6-binding peptide (αvβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin αvβ6-selective internalization, cell binding, and cytotoxicity. Integrin αvβ6-selective tumor accumulation of the [64Cu]PDC-1 was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of mice bearing αvβ6 (+) tumors (median survival: 77 days, vs αvβ6 (-) tumor group 49 days, and all other control groups 37 days).

Cardiac malformations are sporadically diagnosed in domestic species; however, little literature is available for this group of developmental anomalies in goats. We performed a retrospective study to catalog congenital cardiac conditions in goats submitted to the University of California-Davis, Veterinary Medical Teaching Hospital, Anatomic Pathology Autopsy Service. From 2000 to 2021, of 1,886 goat autopsies, 29 cases of cardiac malformations were identified (1.5%). Thirteen were ≤ 2-wk-old, 8 were 1-6-mo-old, and 8 were adults 2-9-y-old. The most common malformations were ventricular septal defect (VSD; 21 of 29), atrial septal defect or persistent foramen ovale (10 of 29), and double-outlet right ventricle (3 of 29). Nine cases had > 1 malformation, typically including a VSD. Conditions that had not been reported in the goat included double-outlet right ventricle (3), tetralogy of Fallot (1), cor triatriatum sinister (1), and mitral valve dysplasia (1). Two adult cases were incidental and not suspected clinically. Cardiac malformations occur not uncommonly in goats and should be considered in a wide age range.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P

The pandemic caused a new digital scheme of work to be implemented in higher educational institutes to avoid physical contact, which is referred to as emergency remote teaching in the literature (Hodges, Moore, Lockee, Trust, & Bond, 2020). The inevitable consequence of emergency remote teaching (later on ERT) was that the students' inter-and extra organisational relationships decreased significantly (Pusztai & Gy}ori, 2021). Based on the results of previous studies, we know that the lack of student relationships is strongly related to ineffectiveness (Astin, 1993; Pusztai, 2015; Tinto, 1975), which was also identified during the period of ERT (Pusztai & Gy}ori, 2021). In the current study, firstly, we hypothesised that the students' social interactions, which were accomplished by video gaming, could compensate for isolation (Pisan, 2007) and improve their effectiveness. Secondly, we hypothesised that video gaming might prove ineffective due to stressful and uncertain periods as well as avoidance of activity. In our study, we applied database analysis (Learning Alone database, N 5 677) and half-structured interviews (N 5 19). In the quantitative sample, we identified that increased gaming time (compared to the time spent before the pandemic) was related to persistence reduction, whereas similar results were obtained with the reduced playing time. In addition, the interview participants reinforced that they used video gaming as a tool to maintain their relationships during ERT, and they tended to do so in their relationships with other students as well. Thus it can be said that video gaming is an extracurricular activity that could affect academic effectiveness positively and negatively at the same time.

Pulmonary veno-occlusive disease has a significantly worse prognosis than idiopathic pulmonary arterial hypertension. According to a case series from France, the median survival time from diagnosis to death or lung transplantation was only 1 year, and in a more recent analysis, pulmonary arterial hypertension therapy had no significant effect on survival. There are case reports and case series describing both beneficial and adverse effects of pulmonary arterial hypertension-related medications. The most life-threatening complication of such a therapy is pulmonary oedema. In the long term, lung transplantation remains the best treatment option for suitable patients. However, elderly patients with concomitant or precipitating malignant disease are not considered transplant candidates. We describe a 59-year-old pulmonary veno-occlusive disease patient with multiple myeloma in World Health Organisation functional class IV who was successfully treated with sildenafil for almost 5 years.

Arctic ecosystems are especially vulnerable to the impacts of climate change because of the limit to possible northward shifts for species dependent on land or continental shelf and because the rate of warming of the region has been 2-4 x the global average in recent decades. The decline in sea ice in the Arctic has both direct and indirect impacts on the species that live in association with ice, breeding on it, traveling over it, feeding on other ice-dependent species or avoiding competition with subarctic species that cannot exploit resources in ice-covered areas. Herein, we present a metamodel of a top-level predator, the polar bear (Ursus maritimus), and two of its key prey species, ringed seals (Pusa hispida) and bearded seals (Erignathus barbatus), which are important in maintaining current polar bear densities and in turn are strongly influenced by bear predation. We used a metamodel that links Population Viability Analyses of the three species in order to examine how the impacts of declining spring land-fast sea ice on the fjords of Svalbard (Norway) and Frans Josef Land (Russia) can cascade through this predator-prey system. As the ice conditions that allow ringed seals to raise pups in snow-covered lairs on the frozen fjords diminish, or even disappear, ringed seal populations using the land-fast sea ice will collapse due to lack of successful recruitment. Consequently, the polar bear population, which relies heavily on hunting ringed seals in the land-fast sea ice to be able to raise their own offspring is also likely to decline. Our models suggest time-lags of decades, with the polar bear population not entering into decline until the lack of recruitment of ringed seals results in the depletion of breeding age ringed seals – starting in the third decade from the start point of the model and dropping below the initial population size only some decades later. Although lags between climate change and impacts on the ice-associated fauna are expected, the sea ice conditions have already changed dramatically in the northern Barents Sea region, including the Svalbard Archipelago, and the collapse of this Arctic species assemblage might already be underway.

Inflammasome activation is a robust innate immune mechanism that promotes inflammatory responses through the release of alarmins and leaderless cytokines, including IL-1α, IL-1β, and IL-18. Various stimuli, including infectious agents and cellular stress, cause inflammasomes to assemble and activate caspase-1. Then, caspase-1 cleaves targets that lead to pore formation and leaderless cytokine activation and release. Toxoplasma gondii has been shown to promote inflammasome formation, but the cell types utilizing caspase-1 and the downstream effects on immunological outcomes during acute in vivo infection have not been explored. Here, using knockout mice, we examine the role of caspase-1 responses during acute T. gondii infection globally and in Cx3cr1-positive populations. We provide in vivo evidence that caspase-1 expression is critical for, IL-18 release, optimal interferon-γ (IFN-γ) production, monocyte and neutrophil recruitment to the site of infection, and parasite control. Specifically, we find that caspase-1 expression in Cx3cr1-positive cells drives IL-18 release, which potentiates CD4+ T cell IFN-γ production and parasite control. Notably, our Cx3cr1-Casp1 knockouts exhibited a selective T cell defect, mirroring the phenotype observed in Il18 knockouts. In further support of this finding, treatment of Cx3cr1-Casp1 knockout mice with recombinant IL-18 restored CD4+ T cell IFN-γ responses and parasite control. Additionally, we show that neutrophil recruitment is dependent on IL-1 receptor accessory protein (IL-1RAP) signaling but is dispensable for parasite control. Overall, these experiments highlight the multifaceted role of caspase-1 in multiple cell populations contributing to specific pathways that collectively contribute to caspase-1 dependent immunity to T. gondii.

Abstract Throughout the Arctic, ice‐affiliated marine mammals constitute local subsistence resources but detrimental effects of declines in their sea ice habitats create a need for harvest sustainability assessments in light of climate change. At the same time, empirical data required for thorough population analysis of these species are often sparse at best, as illustrated by the focal species in this study, ringed seals in Svalbard: the last population survey took place two decades ago (2002–2003), demographic data are limited to age, sex, and reproductive status of a small subset of shot individuals, and harvest reporting is patchy and incomplete. Data sparsity is one of the main reasons why potential biological removal (PBR) became a commonly used tool for assessing sustainability of marine mammal harvests. Herein, we calculated PBR for Svalbard ringed seals using both recommended default parameters and population‐specific parameters obtained from an integrated population model (IPM). PBR estimates were highly uncertain, suggesting the number of sustainably harvestable individuals could lie anywhere between 0 and 91, with a substantial chance of any harvest being unsustainable under current environmental conditions and trends. Subsequent population viability analyses (PVAs) further confirmed that the current harvest was likely unsustainable, even in a scenario in which sea ice conditions would not deteriorate (and therefore lower pup survival) further. However, uncertainty in population projections was high, and forecasts thus not ideal for formulating management advice. Better forecasts will require more frequent population surveys and obtaining more knowledge regarding the links between vital rates and environmental conditions, both of which may be facilitated by the adoption of novel technology (e.g., drone monitoring, genetic studies). The modeling framework created in this study can be readily updated with new data as they become available, and can serve as a tool for adaptive management of this and other marine mammal populations.

Climate change is impacting marine ecosystems throughout the circumpolar Arctic, altering seasonal habitats and the food bases for fishes, seabirds, and marine mammals. Arctic and Subarctic regions provide resources for resident species and for species that migrate to the north from more southerly regions. Changes in northerly latitudes thus impact endemic as well as non-endemic animals. Herein, we review what is known about climate-driven changes in the migration patterns of Arctic and Subarctic marine vertebrates, including: 1) Arctic residents with seasonal movements – those fishes, seabirds, and marine mammals that complete their entire life cycle within the Arctic but exhibit seasonal movements; 2) Breeding migrants – many seabirds enter the Arctic to breed and subsequently migrate south in the fall; and 3) Summer visitors for feeding – certain species of boreal fishes, seabirds and marine mammals arrive during the northern summer to feed on abundant prey though they breed elsewhere. Migratory movements are often driven by the timing and extent of sea ice, which defines suitable habitat for some animals and limits access to open water and prey for others. Longer open-water seasons, warmer ocean temperatures, and stronger winds have resulted in earlier production blooms in spring and often, extended open-ocean plankton blooms into late summer, resulting in altered prey types and distributions. A common thread among taxa is that shifts in distribution and timing of migrating animals indicate they are traveling farther north, or shifting longitudinally, and migrations are occurring over longer seasonal time frames. Species performing multiple lifetime migrations or long-distance migrants may need to adjust migration timing or routing iteratively to match changes in marine productivity. Altered animal distributions or phenology, and reduced sea ice, affects access to animals that are critical nutritional, economical, and cultural components of Indigenous people’s lives in the Arctic. Ongoing changes challenge the resilience and adaptability of Arctic people and ecosystems, and will require adaptive research and management approaches.

Everyday life requires an adaptive balance between distraction-resistant maintenance of information and the flexibility to update this information when needed. These opposing mechanisms are proposed to be balanced through a working memory gating mechanism. Prior research indicates that obesity may elevate the risk of working memory deficits, yet the underlying mechanisms remain elusive. Dopaminergic alterations have emerged as a potential mediator. However, current models suggest these alterations should only shift the balance in working memory tasks, not produce overall deficits. The empirical support for this notion is currently lacking, however. To address this gap, we pooled data from three studies (N = 320) where participants performed a working memory gating task. Higher BMI was associated with overall poorer working memory, irrespective of whether there was a need to maintain or update information. However, when participants, in addition to BMI level, were categorized based on certain putative dopamine-signaling characteristics (single-nucleotide polymorphisms [SNPs]; specifically, Taq1A and DARPP-32), distinct working memory gating effects emerged. These SNPs, primarily associated with striatal dopamine transmission, appear to be linked with differences in updating, specifically, among high-BMI individuals. Moreover, blood amino acid ratio, which indicates central dopamine synthesis capacity, combined with BMI shifted the balance between distractor-resistant maintenance and updating. These findings suggest that both dopamine-dependent and dopamine-independent cognitive effects exist in obesity. Understanding these effects is crucial if we aim to modify maladaptive cognitive profiles in individuals with obesity.

BackgroundTransition from pediatric to adult health care varies and is resource intensive. Patient-centered health information technology (HIT) interventions are increasingly being developed in partnership with patients. ObjectiveThis study aims to develop an internet-based mobile app intervention for patients with brain-based disabilities to improve transition in care readiness. MethodsThe app was designed for patients aged 15 to 17 years with brain-based disabilities having the ability to use a mobile app. A multidisciplinary team, an industry partner, and a patient and family advisory council was assembled. We hypothesized that existing tools could be migrated into the app to address education, empowerment, and navigation. We used cognitive learning theory to support chapters targeting transition in care skill sets. We used the agile iterative methodology to engage stakeholders. ResultsWe developed a novel MyREADY Transition HIT platform. An electronic mentor supported cognitive learning with messaging, quizzes, rewards, and videos. We used gaming to guide navigation through a fictitious health care city. Adapting existing tools was achieved by the patient and family advisory council requesting personalization. Our iterative design required time-consuming back-end technology management. Developing the platform took 24 months instead of our grant-approved 12 months, impacting the onset of the planned trial within the allotted budget. ConclusionsA novel patient-centered HIT platform to improve health care transition was successfully developed in partnership with patients and industry. Careful resource management was needed to achieve timely delivery of the end product, flagging the cautious planning required to deliver HIT tools in time for the much-needed trials informing their clinical application. Trial RegistrationClinicalTrials.gov NCT03852550; https://clinicaltrials.gov/study/NCT03852550

Abstract Introduction Rural cancer caregivers experience obstacles in accessing services, obtaining respite, and ensuring their care recipients receive quality care. These challenges warrant opportunities to participate in evidence‐based behavioral intervention trials to fill support gaps. Adaptation to rural settings can facilitate appropriate fit, given higher caregiver service needs and unique challenges. We present findings from the adaptation process of a psychoeducational intervention designed to support cancer caregivers in rural settings. Methods We adapted Reblin's CARING intervention, designed for neuro‐oncology, to target caregivers of rural cancer patients across cancer sites. First, we conducted formative work to determine the unmet social and supportive care needs rural cancer caregivers faced. We used the Framework for Reporting Adaptations and Modifications to Evidence‐based Implementation Strategies (FRAME‐IS) to guide the modifications. To conduct the adaptation, we elicited feedback through qualitative interviews of seven caregivers and three cancer hospital staff and thematic analysis to inform intervention modifications. Our qualitative study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ). Results Interviews revealed that service access was a pressing need, along with financial (e.g., treatment costs, employment challenges) and geographic barriers (e.g., distance to treatment, road conditions). We modified content, training, and context using the FRAME‐IS steps. Changes enhanced fit through the following adaptations: changes to social support domains, session content, interventionist training, resource offerings, screening and recruitment processes, and virtual delivery. Discussion Challenges to establishing successful psychosocial oncology interventions may be improved through participant‐centered approaches and implementation science. Additional systemic challenges, including lack of systematic documentation of caregivers, persist and may especially disadvantage under‐represented and underserved groups, such as rural dwellers. The enCompass intervention is undergoing ongoing single‐arm pilot of rural cancer patient/caregiver dyads targeting caregiver coping self‐efficacy and patient/caregiver distress (Clinical Trials #NCT05828927).

BackgroundLimited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome.MethodsPCR-positive SARS-CoV-2 patients, enrolled in a natural history study, underwent analysis of the plasma proteome. A prospective cohort of 66 unvaccinated and 24 vaccinated persons with different degrees of infection severity were evaluated acutely (within 40 days of symptom onset), and at three and ten months. Comparisons based on vaccination status alone and unsupervised hierarchical clustering were performed. A second cohort of vaccinated Omicron patients were evaluated acutely and at ten months.ResultsAcutely, unvaccinated patients manifested overexpression of proteins involved in immune and inflammatory responses, while vaccinated patients exhibited adaptive immune responses without significant inflammation. At three and ten months, only unvaccinated patients had diminished but sustained inflammatory (C3b, CCL15, IL17RE) and immune responses (DEFA5,TREM1). Both groups had underexpression of pathways essential for cellular function, signaling, and angiogenesis (AKT1, MAPK14, HSPB1) across phases. Unsupervised clustering, based on protein expression, identified four groups of patients with variable vaccination rates demonstrating that additional clinical factors influence the plasma proteome. The proteome of vaccinated Omicron patients did not differ from vaccinated pre-Omicron patients.ConclusionsVaccination attenuates the inflammatory response to SARS-CoV-2 infection across phases. However, at ten months after symptom onset, changes in the plasma proteome persist in both vaccinated and unvaccinated individuals, which may be relevant to post-acute sequelae of SARS-CoV-2 and other viral infections associated with post-acute infection syndromes.

Rationale: Severe pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is currently defined by an elevated mean pulmonary arterial pressure and strongly elevated pulmonary vascular resistance >5 wood units. Clinically, these patients show a male predominance, and usually present with very severe dyspnea, severe hypoxemia, strongly decreased exercise capacity and poor prognosis, even though the clinical picture is frequently associated with less severe airflow obstruction. Explanted lung samples of patients with COPD and severe PH show severe remodeling of small pulmonary arterioles, predominantly in the intima and media of the vessels. In this concise review, we discuss the clinical and histopathological evidence of severe PH in COPD.

BackgroundThe trajectory of liver fibrosis is not well understood in the contemporary era of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) therapy.MethodsWe assessed the Enhanced Liver Fibrosis (ELF) score, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) in 116 women with HIV/HCV coinfection over a 4-year period. Random-effects linear regression models examined the rate of fibrosis change 1-2 years before starting HCV treatment, within 1 year before starting (peri-HCV treatment), within 1 year after and 1-2 years post-HCV treatment in unadjusted and adjusted models including age, race, and changes from pretreatment of factors that might affect fibrosis (eg, alcohol, integrase strand inhibitor [INSTI] use, waist circumference, CD4 count).ResultsINSTI use nearly doubled from pre- to peri-HCV treatment. In unadjusted analysis, there was a 3.3% rate of rise in ELF pre-HCV treatment, 2.2% and 3.6% rate of decline during the peri- and 1-year post-HCV treatment period, respectively, followed by a 0.3% rise. Similar findings were observed for APRI and FIB-4. There was little effect on the estimated fibrosis trajectories after adjustment.ConclusionsThe apparent lack of decline in biomarkers of liver fibrosis beyond 1 year after HCV cure suggests that continued monitoring of liver fibrosis and interventions to mitigate progression in people with HIV after HCV cure remains essential.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with different infectivity, transmission potential, and morbidity change the characteristics of local epidemics and affect vaccine effectiveness. As part of the University of Southern California COVID-19 Pandemic Research Center's efforts to understand, control, and inform local community on coronavirus disease 2019 (COVID-19), we implemented a SARS-CoV-2 surveillance program among students, employees, and USC Keck Medical Center patients. We present the epidemiology and distribution of SARS-CoV-2 and its variants among the population.MethodsWe used digital droplet reverse-transcriptase polymerase chain reaction (PCR) to analyze in real-time remnant SARS-CoV-2 PCR-positive saliva specimens stored at the USC Keck Medicine laboratory between September 2020 and April 2022. Samples were tested for the original strain (A20) and 9 SARS-CoV-2 variants: α(B.1.1.7, Q.1-Q.8), β(B.1.351, B.1.351.2, B.1.351.3), γ(P.1, P.1.1, P.1.2), δ(B.1.617.2), δ+(or δ417N), ε(B.1.427 and B.1.429), η(B.1.525), λ(C.37) and ο(B.1.1.529, ΒΑ.1, BA.2). We reviewed deidentified health information from positive cases including demographics, history of COVID-19 (eg, symptoms, hospitalizations, and repeat infections), and COVID-19 vaccination status.ResultsWe reviewed 1169 cases and determined the variant type of 482 specimens: 77 specimens were original strain, 119 "Delta", 165 "Omicron". The original strain was detected during the third and fourth quarters of 2020. The Delta variant appeared during the second quarter of 2021, whereas Omicron appeared in the fourth quarter of 2021.ConclusionsProspectively tracking SARS-CoV-2 variants in a university population and a hospital system, utilizing a low-cost, high-throughput PCR assay, was feasible. Local variant monitoring remains important to inform prevention and control efforts among university and clinical settings.

IntroductionThe current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak.Materials and methodsThe data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively.Statistical analysisDescriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables.ResultsClinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p