bluuebunny/crossref_metadata_2025 huggingface dataset:
“Sense of Presence” in Immersive Virtual Reality Environment
Authors: Cypress Brigitte S. , Caboral-Stevens Meriam
Published: July 2022

There is no concept analysis in the literature about “sense of presence” in immersive virtual reality environment in the context of nursing clinical education. The purpose of this article is to explore the meaning and derive an operational definition of the concept of sense of presence within the context of immersive virtual reality environment in nursing clinical education. Using Rodgers' approach, this evolutionary concept analysis will clarify the concept's surrogate and related terms, attributes, antecedents, and consequences. A clearer conceptualization is paramount to help provide knowledge for nurses and other health care professionals, thus guiding their practice, theory, and research.
The Effect of Intensive Care Unit Diaries on Posttraumatic Stress Disorder, Anxiety, and Depression
Authors: Gazzato Arianna , Scquizzato Tommaso , Imbriaco Guglielmo , Negro Alessandra , Caballo Garrido Maria Cristina , Landoni Giovanni , Zangrillo Alberto , Borghi Giovanni
Published: July 2022

Introduction

Patients discharged from the intensive care unit (ICU) suffer from long-term symptoms affecting the physical, psychological, and cognitive well-being and cannot understand memories and dreams. Intensive care unit diaries describe daily events about the patient and may allow them to reconstruct their experience.

Objective

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of ICU diaries on posttraumatic stress disorder (PTSD), depression, and anxiety.

Methods

Five electronic databases were searched up to May 6, 2022. We included RCTs comparing patients admitted to the ICU who received a diary to those who did not receive a diary. The primary outcome was the rate of PTSD. Secondary outcomes were rates of depression and anxiety.

Results

We included 7 RCTs. Patients who received a diary during the ICU admission had reduced rate of PTSD (78/432 [18%] vs 106/422 [25%]; risk ratio [RR], 0.73; 95% confidence interval [CI], 0.57-0.94; P = .02; I
2 = 0%; trial sequential analysis-adjusted CI, 0.55-0.97) when compared with patients who did not receive a diary. We found a non–statistically significant difference toward a reduction in the rate of depression (38/232 [16%] vs 54/224 [24%]; RR, 0.70; 95% CI, 0.49-1.01; P = .06; I
2 = 0%) and anxiety (63/232 [27%] vs 70/224 [31%]; RR, 0.64; 95% CI, 0.29-1.40; P = .26; I
2 = 67%).

Conclusions

Providing an ICU diary to patients admitted to the ICU reduced the rate of PTSD symptoms compared with usual care.
Intensive and Critical Care Nursing of a COVID-19 Patient in Turkey
Authors: Yildirim Dilek , Genc Zeliha
Published: July 2022

Background

A multidisciplinary approach is required to provide holistic care and treatment in the fight against the COVID-19 pandemic. Being in the center of the multidisciplinary approach, nurses provide therapeutic, primary, and psychosocial care for the patients.

Objectives

This study was conducted to diagnose according to the North American Nursing Diagnosis Associations by determining the care needs of a case who was diagnosed with COVID-19, planning interventions, and observing the results.

Methods

This descriptive case study included a patient who applied to a university hospital located in Istanbul/Turkey between March and April 2020 because of COVID-19. As the inclusion criteria, only a positive result from a polymerase chain reaction test was accepted. The details of the patient presented in the study were obtained through face-to-face interviews and electronic medical records.

Discussion

Specified care plans enable defining problems in practice for all needs of the individual and developing solution recommendations. It was observed that there were improvements and a decrease in symptom severity after the interventions were applied for the symptoms developing in the case. The execution of the treatment and care practices under quality and effective nursing care such as giving proper ventilatory support at the right time, giving prone position for a long time, and providing sufficient fluid resuscitation and an early and balanced diet contributed to the patient’s discharge from the intensive care unit successfully without having any organ dysfunction. This presentation is expected to be a source for collaborative nursing care for other cases diagnosed with COVID-19 and intensive care indications.

Conclusions

Nursing care interventions were applied for gas exchange, risk of decreased tissue perfusion, excess fluid volume, and constipation nursing diagnosis. It was observed that there were improvements and a decrease in symptom severity after the interventions were applied for the symptoms developing in the case. This presentation is expected to be a source for collaborative nursing care for other cases diagnosed with COVID-19 and intensive care indications.
Interventions to Reduce Nurses' Moral Distress in the Intensive Care Unit
Authors: Hickey Johannah
Published: July 2022

Background

Critical care nurses experience moral distress, the phenomenon of knowing the “right” thing to do but being unable to do so, at high rates; this contributes to attrition and has severe mental health impacts on nurses.

Objective

The purpose of this integrative review was to determine if interventions to reduce moral distress have an effect on intensive care unit (ICU) nurses' moral distress levels.

Methods

Three databases were searched, PubMed, APA PsycNet, and CINAHL, using the keywords “moral distress” AND nurs* AND reduc* AND (“intensive care” OR “critical care” OR ICU). Only experimental studies involving adult ICU nurses were included for a total of 6 studies.

Results

Interventions fell into 3 categories: (1) educational interventions, (2) interventions to enhance the ICU environment, and (3) interventions to help nurses cope. Two studies detailing educational interventions demonstrated some reduction in moral distress. One study aimed to improve the ICU environment and showed some statistically significant reduction in moral distress. All 6 studies included some focus on coping, and 2 showed statistically significant reductions in moral distress.

Discussion

Only a few studies have been conducted examining this issue. These studies had severe limitations, such as small sample sizes, attrition, and inadequate control groups. There were also few statistically significant results. These interventions should be reexamined using larger sample sizes, and other interventions should also be trialed. COVID-19 may have had a significant impact on this issue, and interventions may need to be refocused in the wake of the pandemic.
Management of Acute and Chronic Pouchitis
Authors: Tome June , Raffals Laura E. , Pardi Darrell S.
Published: July 2022

BACKGROUND:

Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of choice when colectomy is needed for medically refractory ulcerative colitis. Pouchitis is one of the most common complications among patients who have undergone ileal pouch-anal anastomosis and represents a spectrum of disease varying in both phenotype and clinical course.

OBJECTIVE:

The aim of this review is to assist clinicians and surgeons in the treatment of both acute and chronic pouchitis, including newer therapies and future directions.

DIAGNOSIS AND MANAGEMENT:

Diagnosis is made by endoscopy of the pouch with biopsy, since other conditions may produce similar symptoms such as increased stool frequency, abdominal cramps, and urgency. Pouchitis is classified by duration (acute versus chronic), disease pattern (infrequent, relapsing, continuous), and response to antibiotics (responsive, dependent, refractory). The Pouchitis Disease Activity Index may be used to measure disease activity. The management of pouchitis is guided by the disease phenotype. Acute episodes are treated with an initial 2-week course of antibiotics (typically ciprofloxacin or metronidazole), although patients with relapsing or chronic pouchitis may require long-term antibiotic treatment or the cycling of different antibiotics. Certain probiotics may also be used for maintenance therapy in those with chronic symptoms. For patients with chronic antibiotic refractory pouchitis, oral budesonide, immunosuppressive agents (azathioprine), or biologic therapy (infliximab, adalimumab, vedolizumab, ustekinumab) may be required for both induction and maintenance with close monitoring for potential side effects. In rare cases, diverting ileostomy or pouch excision may be required.

CONCLUSION:

Pouchitis represents a spectrum of disease phenotypes, ranging from acute antibiotic responsive pouchitis to chronic antibiotic refractory pouchitis. The management of pouchitis is primarily directed by the disease phenotype.
Bone grafting in maxillofacial trauma
Authors: Gokdogan Ozan
Published: July 2022

Purpose of review

The purpose of this article is to review the recent grafting strategies in maxillofacial trauma.

Recent findings

Recent technological advancements have applications in the management of maxillofacial trauma; advancements in imaging modalities such as 3D imaging can help surgeons in both the preoperative and intraoperative periods. These may be coupled with navigational systems to further facilitate complex reconstructions. 3D printing has been used in reconstruction and 3D, 4D, and 5D bioprinting technologies continue to improve and to find new uses, and stem cells and growth factors in maxillofacial trauma are also among the most studied topics. Maxillofacial traumas have decreased in number during the COVID-19 pandemic, as more conservative approaches have been preferred in COVID pandemic conditions.

Preoperative planning is the most important step in the reconstruction of maxillofacial trauma defects, and early bone and soft tissue reconstructions are recommended in severe maxillofacial traumas. Autogenous grafts are the gold standard in bone grafting. Nonvascularized grafts are planned according to the size, shape, and location of the defect, with vascularized bone flaps preferred in large defects, wide soft tissue defects, and contaminated defects. Alloplastic grafts or xenografts may be used if autogenous grafts are not available.
Alloplastic malar implants in aesthetic facial surgery
Authors: Farhood Zachary , Asaria Jamil
Published: July 2022

Purpose of review

To examine the recent literature on aesthetic alloplastic malar implants.

Recent findings

Alloplastic implantation is heavily favored in the oromaxillofacial literature. Recent articles have examined porous polyethylene and silicone implantation. Overall patient satisfaction is high and complications are low. Outcomes are likely comparable with alternative modalities to rejuvenate the face in the appropriate hands.

Alloplastic implantation continues to be a reliable tool for malar augmentation.
Developments in facial feminization surgery
Authors: Rodman Regina
Published: July 2022

Purpose of review

Facial feminization surgery (FFS) is being performed by facial plastic surgeons with increasing frequency. As insurance companies expand benefits to cover these procedures, more and more institutions are developing programs to treat transgender patients. The purpose of this review is to summarize recent literature on the subject so that those interested in this subject may have a framework to analyze these works.

Recent findings

The most significant findings are that FFS does appear to be safe with low complication rates, despite long operative times due to multiple procedures performed. Much of the recent literature is reviews of each practice's techniques. This is valuable to educate those interested in beginning to perform these surgeries. Further, these reviews can eventually be compiled into a standard of care. Virtual surgical planning is currently being used by some departments, but its value is yet to be determined.

FFS is performed with increasing frequency. Current literature reviews best practices with the goal of eventually establishing a standard of care.
Nonsurgical rhinoplasty: prevention and management of associated complications
Authors: Mella Jeffrey , Oyer Samuel
Published: July 2022

Purpose of review

Nonsurgical rhinoplasty (NSR) continues to grow in demand and popularity. Consequently, there has been a rise in the number of reported complications. This review will summarize and discuss the current evidence for the prevention and management of adverse events related to NSR with a specific emphasis on practical clinical applications. The review is based on recent systematic reviews and multidisciplinary expert consensus recommendations.

Recent findings

First, NSR has overall favorable outcomes with rare complications. Second, vascular compromise is a rare event, but the number of reported severe complications is rising. Third, providers should be intimately familiar with preventive measures, early signs and symptoms, and appropriate management algorithms of all possible complications. Fourth, having a readily available ‘toolbox’ of recommended therapies may improve timely management of emergent complications.

The number of complications associated with NSR is expected to rise congruent with the increased demand for the procedure. Although NSR has a favorable safety profile, complications can occur in the best of hands even when using appropriate risk reduction strategies. Early detection and appropriate treatment of known complications may eliminate or minimize sequelae and allow providers to continue to safely perform NSR.
Noma, a neglected disease: prevention is better than cure
Authors: Farley Elise , Amirtharajah Mohana , Shaye David A.
Published: July 2022

Purpose of review

There is a need for concerted effort to increase Global awareness about noma (cancrum oris). This paper aims to summarize the recent literature on noma and provide suggestions that could be implemented to raise awareness about this neglected disease.

Recent findings

Noma has been recognized, diagnosed and reported for centuries. Despite significant progress in scientific methods over time, the published literature on noma has predominantly been of low level clinical and scientific evidence. Recent studies have reported on noma's global distribution and its predisposing risk factors, its treatment, its knowledge and beliefs and has included a number of literature reviews. Noma cases are being reported from an increasingly diverse set of geographical locations.

Noma has largely been neglected in the research sphere. Noma is a preventable disease and its progression can be halted if patients are recognized and treated in the early stages of disease. Treatment for late stage noma survivors remains complex and time consuming, requiring substantial human and financial resources most commonly not achieving functional and cosmetic anatomy. The ultimate aim is therefore prevention, initiatives should be integrated into existing health programs.
Necrotizing fasciitis of the face: current concepts in cause, diagnosis and management
Authors: Ahmadzada Sejad , Rao Amshuman , Ghazavi Hossein
Published: July 2022

Purpose of review

Necrotizing fasciitis of the face is uncommon but potentially life threatening. With adequate multidisciplinary treatment, mortality and has significantly improved. This article highlights current concepts and supporting literature in the management of facial necrotizing fasciitis.

Recent findings

Management of necrotizing fasciitis involving the face requires a multisciplinary team approach, including early medical and surgical intervention. With early haemodynamic support, broad spectrum antibiotics and aggressive surgical debridement, mortality has reduced significantly. Soft-tissue reconstruction can be effectively utilized once the infection has been adequately treated. Although some adjunctive treatment such as vacuum assisted closure dressing has shown to be of benefit, other treatments such as hyperbaric oxygen remains controversial.

Necrotizing fasciitis is an aggressive soft tissue involving that rapidly spreads along fascial planes. Necrotizing fasciitis involving the face is rare owing to its rich blood supply but is also difficult to manage due to the complex regional anatomy. Common sources are odontogenic, sinugenic, peritonsillar or salivary gland infections and often polymicrobial. The principles of treatment include early and aggressive haemodynamic support, broad spectrum antibiotics and aggressive surgical debridement. Often times repeat debridements following close monitoring is required. Reconstructive options are viable only after the infection has been adequately treated. Although mortality has significantly improved, mediastinal involvement, multiple comorbidities and delayed treatment confers a worse prognosis.
Advances in Pediatric Diagnostic Endoscopy: A State-of-the-Art Review
Authors: Lerner Diana G. , Mencin Ali , Novak Inna , Huang Clifton , Ng Kenneth , Lirio Richard A. , Khlevner Julie , Utterson Elizabeth C. , Harris Brendan R. , Pitman Ryan T. , Mir Sabina , Gugig Roberto , Walsh Catharine M. , Fishman Doug
Published: July 2022

Pediatric endoscopy has revolutionized the way we diagnose and treat gastrointestinal disorders in children. Technological advances in computer processing and imaging continue to affect endoscopic equipment and advance diagnostic tools for pediatric endoscopy. Although commonly used by adult gastroenterologists, modalities, such as endomicroscopy, image-enhanced endoscopy, and impedance planimetry, are not routinely used in pediatric gastroenterology. This state-of-the-art review describes advances in diagnostic modalities, including image-enhanced endoscopy, confocal laser endomicroscopy, optical coherence tomography, endo functional luminal imaging probes, wireless motility/pH capsule, wireless colon capsule endoscopy, endoscopic ultrasound, and discusses the basic principles of each technology, including adult indications and pediatric applications, safety cost, and training data.
Juvenile Hemochromatosis in an Asymptomatic Patient—Importance of Early Diagnosis
Authors: Nashed Bola , Fonseca Carolina , Vander Pols William , Kumar Sanjay , Lyons Hernando , Berman Brian , Guzzardo Gianna M.
Published: July 2022

Juvenile hemochromatosis is a rare inherited disorder of iron regulation leading to iron overload, which usually presents before the age of 30. One of the most serious clinical characteristics associated with early-onset iron overload is liver disease with eventual cirrhosis, often associated with a reduced life expectancy even after treatment. This case report summarizes an asymptomatic pediatric patient with persistently elevated transaminase levels, which led to a diagnosis of juvenile hemochromatosis relatively early in the course of his disease. The aim of this case report is to increase awareness and stress the importance of early diagnosis and treatment, as it is vital to prevent life-threatening complications and optimize patient outcomes. Consideration should be taken to recognize potential manifestations despite the rarity of the condition. Patients with signs of hepatocellular injury without explanation should prompt evaluation including consideration for iron overload after other common causes are ruled out.
Assessing Barriers to use of the Specific Carbohydrate Diet in Pediatric Inflammatory Bowel Disease: A Qualitative Study
Authors: Schwartz Naomi R.M. , McNichol Savannah R. , Devine Beth , Phipps Amanda I. , Roth Joshua A. , Suskind David L.
Published: July 2022

Objectives:

Because of the high cost and associated toxicities of pharmacotherapy treatment for inflammatory bowel disease (IBD), there has been growing interest in dietary therapy. The objective of this study is to assess barriers to initiating or maintaining the specific carbohydrate diet (SCD) to inform strategies for improving access and adherence to the diet.

Methods:

We conducted semistructured interviews with parents of 10 children with IBD receiving care at a single academic treatment center. Parents were eligible if their child with IBD was either currently on the SCD, previously on the SCD, or opted not to initiate the SCD. Core questions were developed in conjunction with IBD clinical experts. Interviews were transcribed and analyzed using an inductive approach.

Results:

Parents of children diagnosed with IBD primarily chose to try the SCD because of concerns about medication safety. Three major barriers to utilizing the SCD emerged: cost, time commitment, and psychosocial impact. Many parents also expressed that following the SCD got easier over time and some parents experienced spillover effects of improved personal health and understanding of nutrition. All parents were strong proponents of the importance of diet in managing IBD and expressed desire for more research into the SCD and other forms of dietary therapy.

Conclusions:

These findings provide important insight into factors affecting utilization of the SCD in pediatric IBD. Further research is needed to develop interventions or strategies to diminish these barriers and enable more patients to benefit from the SCD.
Probability of Medication Intensifications in Rheumatoid Arthritis Patients With Low Disease Activity Scores on Their Patient-Reported Outcomes
Authors: Seppen Bart Fabian , Verkleij Simone J. , Wiegel Jimmy , ter Wee Marieke M. , Nurmohamed Michael T. , Bos Wouter H.
Published: July 2022

Background

Patients with rheumatoid arthritis require frequent consultations to monitor disease activity and intensify medication when treatment targets are not met. However, because most patients are in remission during follow-up, it should be possible to reduce the number of consultations for them. Electronic patient-reported outcomes (ePROs) could be used to identify patients who meet their treatment goal and who could therefore be eligible to skip their visit.

Objective

The aim of this study was to assess the probability that patients with low disease activity scores on their ePROs do not need a disease-modifying antirheumatic drug (DMARD) or steroid intensification in the first 2 weeks after completion of the ePROs.

Methods

This medical-records review study compared results of ePROs answered during routine care with DMARD or steroid intensifications collected from anonymized electronic medical record at Reade. The primary outcome was the positive predictive value (PPV) of having a low disease activity score on an ePRO for not receiving a DMARD or steroid intensifications within 2 weeks. The 3 studied ePROs (and respective low disease activity outcome) were the Routine Assessment of Patient Index Data 3 (RAPID3) (score <2), Patient Acceptable Symptom State (PASS) (yes), and the flare question (no). The secondary aim of the study was to assess which combination of ePROs resulted in the best PPV for DMARD or steroid intensifications.

Results

Of the 400 randomly selected records, ultimately 321 were included (302 unique patients). The PPV of a RAPID3 <2, being in PASS, and a negative answer on the flare question were, respectively, 99%, 95%, and 83% to not receive a DMARD or steroid intensification within 2 weeks. The combination of a RAPID3 <2 and a negative flare question resulted in a PPV of 100%; this combination was present in 29% (93/321) of the total study population.

Conclusion

The RAPID3, PASS, and flare question have a high diagnostic accuracy to identify individuals who will not receive a DMARD or steroid intensification in the following 2 weeks. The combination of the RAPID3 and flare question yielded the best combination of diagnostic accuracy and highest percentage of patients who could be eligible to skip a visit. These results suggest that accurate identification of patients who meet their treatment goal with ePROs is possible.
Ambulatory Blood Pressure Patterns in Children, Adolescents, and Young Adults With Childhood-Onset Systemic Lupus Erythematosus and Normal Office Blood Pressure
Authors: Mazo Alexandra , Duong Minh Dien , Sharma Madhu , Mahgerefteh Joseph , Goilav Beatrice
Published: July 2022

Objective

Cardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Hypertension (HTN) and nondipping are modifiable risk factors for cardiovascular disease. Limited studies are available for childhood-onset SLE (cSLE). We aimed to assess ambulatory blood pressure monitoring (ABPM) pattern in cSLE patients with normal office blood pressure.

Methods

This cross-sectional single-center study enrolled 25 patients with cSLE, normal office blood pressure and normal renal function. We performed 24-hour ABPM and echocardiography to assess end-organ damage. Descriptive statistics were obtained, and comparison of variables using Fisher exact test, t test, and Mann-Whitney U test was performed to identify potential risk factors for nondipping.

Results

Of the 25 patients, 22 were women; the median age was 18 years (interquartile range, 16–20 years). Median SLE duration was 4.2 years (interquartile range, 2.9–8.1 years); 18 patients had a history of lupus nephritis (LN). Four patients, 3 of whom had LN, had masked HTN. Fourteen patients (56%) were nondipping. The majority of patients without LN (71%) had a nondipping profile. Echocardiography was done for 15 patients. Left ventricular mass index, relative wall thickness, and ejection fraction were normal in all patients. Ambulatory blood pressure monitoring results led to changes in therapy in 5 patients.

Conclusion

Our data provide evidence of high prevalence of nondipping and masked HTN in patients with cSLE, even in patients without LN. Identifying ABPM abnormalities in these patients could potentially improve outcomes.
Gout Screening Identifies a Large Cardiovascular Population at Increased Risk of Mortality
Authors: Ruiz-Simón Silvia , Calabuig Irene , Gómez-Garberí Miguel , Andrés Mariano
Published: July 2022

Objective

Gout is prevalent in people with cardiovascular disease, although up to a third of the cases remain unregistered. We aimed to assess whether active gout screening in inpatients with cardiovascular events helps identify patients at higher risk of mortality after discharge.

Methods

This study included patients admitted for cardiovascular events. Gout was established by records review and clinical interview. After discharge, electronic medical records were reviewed for mortality and cause of death. The association between gout and subsequent mortality was tested using Cox regression models.

Results

Of 266 recruited patients, 17 were lost to follow-up, leaving a final sample of 249 patients (93.6%). Thirty-six cases (14.5%) were classified as having gout; 13 of these (36.1%) were identified through the interview. Mean follow-up was 19.9 (SD, 8.6) months. Gout significantly increased the risk of all-cause mortality in the overall sample (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.13–3.58) and in the subgroup with a prior diagnosis of gout (HR, 2.89; 95% CI, 1.54–5.41). The adjusted HR for all-cause mortality associated with gout was 1.86 (95% CI, 1.01–3.41). Patients with gout carried an increased risk of both cardiovascular and noncardiovascular deaths; age and chronic kidney disease were mortality predictors within the gout population.

Conclusion

Gout was an independent predictor of subsequent all-cause mortality in patients admitted for cardiovascular events. Active screening for gout allowed the detection of a larger population at high risk of mortality and could help tailor patient management to minimize the cardiovascular impact.
Clinical Characteristics and Classification Criteria Performance in a Single-Center Cohort of 114 Patients With Immunoglobulin G4–Related Disease
Authors: Spandorfer Robert , Ahmad Madiha , Khosroshahi Arezou
Published: July 2022

Introduction/Objectives

Immunoglobulin G4–related disease (IgG4-RD) is a heterogeneous fibroinflammatory condition. The 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for IgG4-RD were published to provide unified classification criteria in clinical research. The purpose of this study was to characterize demographics, disease manifestations, and treatments of patients with IgG4-RD and assess performance of the Classification Criteria in a heterogeneous cohort with a large population of Black patients.

Methods

This was a medical records review of all patients referred to a specialized IgG4-RD clinic. Demographics, serology, histopathology, disease manifestations, and treatment information were collected and analyzed. An ACR/EULAR Classification Criteria score for IgG4-RD was calculated to compare performance in definite diagnosis, probable diagnosis, and mimicker groups.

Results

A total of 198 patients were evaluated. Eighty-five (43%) were mimickers. Of the remaining 114, 58 (51%) were classified as definite, and 56 (49%) as probable cases by treating clinicians. Pancreatitis was the most common presentation (37%) among 28 different organ manifestations of IgG4-RD. In patients with definite clinical diagnosis of IgG4-RD, 84% met the IgG4-RD Classification Criteria (i.e., score ≥20) with mean score of 29. Only 9% of the probable cases met this threshold with an average score of 8. None of the mimickers met the Classification Criteria.

Conclusions

This study highlights the broad spectrum of IgG4-RD and validates the use of the ACR/EULAR Classification Criteria for IgG4-RD, including a large proportion of Black patients. As shown in this study, IgG4-RD is a heterogeneous disease and continues to represent a diagnostic challenge to clinicians.
The roles of unrecognized monkeypox cases, contact isolation and vaccination in determining epidemic size in Belgium. A modelling study
Authors: Van Dijck Christophe , Hens Niel , Kenyon Chris , Tsoumanis Achilleas
Published: July 2022

We used a network model to simulate a monkeypox epidemic among men who have sex with men. Our findings suggest that unrecognized infections have an important impact on the epidemic, and that vaccination of individuals at highest risk of infection reduces epidemic size more than post-exposure vaccination of sexual partners.
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Tyrol, Austria: Updated analysis involving 22,607 blood donors covering the period October 2021 to April 2022
Authors: Seekircher Lisa , Siller Anita , Astl Manfred , Tschiderer Lena , Wachter Gregor A. , Pfeifer Bernhard , Huber Andreas , Gaber Manfred , Schennach Harald , Willeit Peter
Published: July 2022

Background

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies.

Methods

We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%).

Results

Median age of participants was 45.3 years (IQR: 30.9-55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8–86.0%) to 95.8% (94.9–96.4%) and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271–296) to 1437 (1360–1518) BAU/mL. The percentages of participants in categories with undetectable levels, and detectable levels at <500, 500–<1000, 1000–<2000, 2000–<3000, and ≥3,000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2–19.9; p-value < 0.001).

Conclusion

Anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.
Cognitive training and remediation interventions for substance use disorders: A Delphi consensus study
Authors: Verdejo-Garcia Antonio , Rezapour Tara , Giddens Emily , Zonoozi Arash Khojasteh , Rafei Parnian , Berry Jamie , Caracuel Alfonso , Copersino Marc L. , Field Matt , Garland Eric L. , Lorenzetti Valentina , Malloy-Diniz Leandro , Manning Victoria , Marceau Ely M. , Pennington David L. , Strickland Justin , Wiers Reinout , Fairhead Rahia , Anderson Alexandra , Bell Morris , Boendermaker Wouter J. , Brooks Samantha , Bruno Raimondo , Campanella Salvatore , Cousijn Janna , Cox Miles , Dean Andrew C. , Ersche Karen D , Franken Ingmar , Froeliger Brett , Gamito Pedro , Gladwin Thomas E. , Goncalves Priscila D. , Houben Katrijn , Jacobus Joanna , Jones Andrew , Kaag Anne M. , Lindenmeyer Johannes , McGrath Elly , Nardo Talia , Oliveira Jorge , Pennington Charlotte R. , Perrykkad Kelsey , Piercy Hugh , Rupp Claudia I , Schulte Mieke H. J. , Squeglia Lindsay M. , Staiger Petra , Stein Dan J , Stein Jeff , Stein Maria , Stoops William W. , Sweeney Mary , Vo Hoa , Witkiewitz Katie , Woods Steven P , Yi Richard , Zhao Min , Ekhtiari Hamed
Published: July 2022

Background and Aims

Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.

Design

Delphi approach with two sequential phases: survey development and iterative surveying of experts.

Setting

Online study.

Participants

During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n=53) identified via recommendations from the Steering Committee and a systematic review.

Measurements

Survey with 67 items covering four key areas of intervention development, i.e., targets, intervention approaches, active ingredients, and modes of delivery.

Findings

Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions, and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training, and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias-modification, goal setting, strategy learning, and meta-awareness as active ingredients; and (iv) both addiction treatment workforce and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities.

Conclusions

Expert recommendations on cognitive training and remediation for SUD highlight the relevance of targeting implicit biases, reward, emotion regulation, and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.
Indoor air pollutants and respiratory outcomes among residents of an informal urban setting in Uganda: a cross-sectional study
Authors: Wafula Solomon T. , Nalugya Aisha , Mendoza Hilbert , Kansiime Winnie K , Ssekamatte Tonny , Walekhwa Abel Wilson , Mugambe Richard K. , Walter Florian , Ssempebwa John C , Musoke David
Published: July 2022

Background

Indoor air pollutants (IAP) such as particulate matter (PM) and carbon monoxide (CO) are a leading cause of acute respiratory symptoms, and long-term health impacts such as respiratory diseases, heart diseases and cancers. In Uganda, literature on the effects of IAP on respiratory outcomes in informal settlements is limited. This study investigated the association of selected IAPs and cooking fuels with respiratory symptoms among children and adults.

Methods

This study was conducted among 284 households in an informal settlement in Uganda from April to May 2022. Information on indoor air conditions, fuel type and adults reported the respiratory symptoms of their children as well as their respiratory symptoms within the previous 30 days. Same-day concentrations of PM less than 2.5 μm (PM2.5) and less than 10 μm(PM10) in diameter were monitored from 9 am to 2 pm using Temptop M2000c 2nd edition particle sensor while CO was measured using a carbon monoxide meter. Robust Poisson regression was used to model the associations between indoor air conditions, fuel type and respiratory health outcomes.

Results

Approximately 94.7% of the households were using biomass fuels. Cough (66.2%), shortness of breath (33.5%) and phlegm (17.6%) were common respiratory symptoms in adults while in children, morning cough (80.0%), day or night cough (34.4%) and shortness of breath (26.5%) were reported. The median PM2.5, PM10 and CO levels were 49.5(IQR= 31.1, 86.2) µg/m3, 73.6(IQR= 47.3,130.5) µg/m3 and 7.7(IQR= 4.1,12.5) ppm respectively. Increase in humidity was associated with higher levels of PM2.5 (ß = 2.74, p =0.004) and PM10 (ß= 4.14, p =0.002) however temperature increases were associated with lower levels of PM2.5 (ß = -11.72, p =0.009) and PM10 (ß= -16.36, p =0.008) but higher CO levels (ß=2.24, p = 0.032). Use of less polluting fuels such as electricity and gas were associated with low levels of PM2.5 (ß= -31.36, 95%CI =-60.7 – -2.02) while home dampness (ß = 3.39, 95%CI =0.07 – 6.72) was associated with higher indoor CO levels. Dampness was associated with acute phlegm in adults (PR= 2.78, 95%CI =1.57 – 4.90) and outdoor cooking was found to be associated with lower shortness of breath risk (PR = 0.60,95%CI =0.40 – 0.91).

Conclusion

The prevalence of respiratory problems among adults and children was high. Poor indoor air conditions were associated with respiratory symptoms in adults and children. Efforts should be made to protect adults and children from the adverse effects of indoor air pollution.
Accurate prognosis for localized prostate cancer through coherent voting networks with multi-omic and clinical data
Authors: Pellegrini Marco
Published: July 2022

Background

Prostate cancer is a very heterogeneous disease, from both a clinical and a biological/biochemical point of view, which makes the task of producing a stratification of patients into risk classes remarkably challenging. In particular, it is important an early detection and discrimination of the more indolent forms of the disease, from the more aggressive ones, requiring closer surveillance and timely treatment decisions.

Methods

We extend a recently developed supervised machine learning (ML) technique, called coherent voting networks (CVN) by incorporating novel model-selection technique to counter model overfitting. The CVN method is then applied to the problem of predicting an accurate prognosis (with a time granularity of 1 year) for patients affected by prostate cancer. The CVN is developed on a discovery cohort of 495 patients from the TCGA-PRAD collection, and validated on several other independent cohorts, comprising a gross total of 744 patients.

Findings

We uncover seven multi-gene fingerprints, each comprising six to seven genes, and a mixed clinical and genomic 5-marker fingerprint, that correspond to different input data types (clinical, mRNA expression, proteomic assays, methylation) and different time points, for the event of post-surgery progression-free survival (PFS) in patients diagnosed with prostate adenocarcinoma, who had not received prior treatment for their disease.

With a mixed 5-marker genomic and clinical fingerprint comprising Gleason primary score, tumor stage, psa, and molecular protein expression levels for CDKN1B and NF2 we attain on three independent cohorts statistically significant AUC values of 0.85, 0.88, and 0.87 respectively for PFS prediction at 3 years.

For purely genomic fingerprints, in seven independent cohorts for 21 combinations of cohort vs fingerprint, we report Odds Ratios ranging from a minimum of 9.0 and a maximum of 40.0, with average 17.5, geometric mean p-value 0.003; Cohen’s kappa values ranging from a minimum of 0.18 to a maximum of 0.65, with average 0.4; and AUC ranging from a minimum of 0.61 to a maximum of 0.88, with average 0.76, geometric mean p-value 0.001, for PFS prediction at 2, 3, and 4 years.

Many of the genes in our fingerprint have recorded prognostic power in some form of cancer, and have been studied for their functional roles in cancer on animal models or cell lines.

Interpretation

The development of novel ML techniques tailored to the problem of uncovering effective multi-gene prognostic biomarkers is a promising new line of attack for sharpening our capability to diversify and personalize cancer patient treatments. For the challenging problem of discriminating a fine time-scale for aggressive types of localized prostate cancer, we show that it is possible to attain more accurate prognostic predictions, with a granularity within a year, for the post-surgery early years.
Nardilysin-Regulated Scission Mechanism Activates Polo-like Kinase 3 to Suppress the Development of Pancreatic Cancer
Authors: Fu Jie , Ling Jianhua , Li Ching-Fei , Tsai Chi-Lin , Yin Wenjuan , Hou Junwei , Chen Ping , Cao Yu , Kang Ya’an , Sun Yichen , Xia Xianghou , Furukawa Kenei , Lu Yu , Wu Min , Huang Qian , Yao Jun , Hawke David H. , Pan Bih-Fang , Zhao Jun , Huang Jiaxing , Wang Huamin , Bahassi EI Mustapha , Stambrook Peter J. , Huang Peng , Fleming Jason B. , Maitra Anirban , Tainer John , Hung Mien-Chie , Chiao Paul J.
Published: July 2022

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of apoptotic pathways. Here, we find that development of anoikis resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often reduced Plk3 expression in human PDAC. Importantly, a 41 kDa Plk3 (p41Plk3) that contained the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase Nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) was quickly removed by proteasome degradation preventing the p41Plk3 inhibition by PBD. We found that p41Plk3 is the activated form of Plk3 that regulates a feedforward mechanism to promote anoikis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn, induces expression of Plk3 and pro-apoptotic genes. These findings uncovered an NRDC-regulated post-translational mechanism (PTM) that activates Plk3, establishing a prototypic regulation by scission mechanism.
LincRNA-Cox2 regulates smoke-induced inflammation in murine macrophages
Authors: Salih Mays Mohammed , Robinson Elektra Kantzari , Malekos Eric , Perez Elizabeth , Capili Allyson , Kim Kihwan , Zhang William Z. , Cloonan Suzanne M. , Carpenter Susan
Published: July 2022

Cigarette smoke (CS) exposure is a risk factor for many chronic diseases including chronic obstructive pulmonary disease (COPD), however the mechanism by which smoke exposure can alter homeostasis and bring about chronic inflammation is poorly understood. Here, we showcase a novel role for smoke in regulating long noncoding RNAs (lncRNAs), showing that it activates lincRNA-Cox2, which we previously characterized as functional in inflammatory regulation. Exposing lincRNA-Cox2 murine models to smoke in vivo confirmed lincRNA-Cox2 as a regulator of inflammatory gene expression in response to smoke both systemically and within the lung. We also report that lincRNA-Cox2 negatively regulates genes in smoked bone marrow derived macrophages exposed to LPS stimulation. In addition to the effects on lncRNAs, we also report dysregulated transcription and splicing of inflammatory protein-coding genes in the bone marrow niche following CS exposure in vivo. Collectively, this work provides insights into how innate immune signaling from gene expression to splicing is altered following in vivo exposure to CS and highlights an important new role for lincRNA-Cox2 in regulating immune genes following smoke exposure.
ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning
Authors: Fäßler Florian , Javoor Manjunath G , Datler Julia , Döring Hermann , Hofer Florian W , Dimchev Georgi , Hodirnau Victor-Valentin , Rottner Klemens , Schur Florian KM
Published: July 2022

Tight regulation of Arp2/3 complex is required to allow productive nucleation of force-generating, branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into Arp2/3 complex. Specifically, both isoforms of the ArpC5 subunit, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. Elevated levels of ArpC5 have also been linked to increased cancer progression and metastasis. Here, we have combined genetic engineering of cells and cellular structural biology to describe how ArpC5 and ArpC5L differentially regulate cell migration. They do so by defining the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, protein dynamics, and actin network ultrastructure. ArpC5 isoforms also have an impact on the positioning of actin assembly factors from the Ena/VASP family, which act downstream of Arp2/3 complex-mediated nucleation. This suggests that ArpC5 and Ena/VASP proteins, both predictors for poor outcome in cancer, are part of a signaling pathway enhancing cell migration and, by inference, metastasis.
Bone marrow AdipoQ-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis and bone mass
Authors: Inoue Kazuki , Xia Yuhan , Qin Yongli , Jiang Jean X. , Greenblatt Matthew B. , Zhao Baohong
Published: July 2022

M-CSF is a critical growth factor for myeloid lineage cells, including monocytes, macrophages and osteoclasts. Tissue resident macrophages in most organs rely on local M-CSF. However, it is unclear what specific cells in bone marrow produce M-CSF to maintain myeloid homeostasis. Here, we identify bone marrow AdipoQ-lineage progenitors, but not bone marrow mature adipocytes or peripheral adipose tissue, as a major cellular source of M-CSF, with these AdipoQ-lineage progenitors producing M-CSF at levels much higher than those produced by osteoblast lineage cells. Deficiency of M-CSF in bone marrow AdipoQ-lineage progenitors drastically reduces the generation of bone marrow macrophages and osteoclasts, leading to severe osteopetrosis in mice. Furthermore, the postmenopausal osteoporosis in a mouse model can be significantly alleviated by the lack of M-CSF in bone marrow AdipoQ-lineage progenitors. Our findings identify bone marrow AdipoQ-lineage progenitors as a major cellular source of M-CSF in bone marrow and reveal their crucial contribution to bone marrow macrophage development, osteoclastogenesis, bone homeostasis and pathological bone loss.