bluuebunny/crossref_metadata_2025 huggingface dataset:
A Community Health Worker Model to Support Hereditary Cancer Risk Assessment and Genetic Testing
Authors: Marsh Leah , Mendoza Marlene , Tatsugawa Zina , Pineda Elizabeth , Markovic Daniela , Holschneider Christine H. , Zakhour Mae
Published: August 2023

OBJECTIVE:

To evaluate the effects of a community health worker–supported hereditary cancer risk-assessment and genetic testing program in a safety-net hospital serving more than 70% medically underserved patients.

METHODS:

This community health worker pilot program began in January 2020 at women’s health clinics by administering original National Comprehensive Cancer Network (NCCN)–based questionnaires. Patients meeting high-risk criteria were offered video-based genetic education and testing, notified of results using telehealth, and offered indicated counseling. We compared the rate of genetic counseling and testing in the first 18 months of the pilot program with that in the prior 18 months.

RESULTS:

In the first 18 months of the pilot program, 940 patients were screened through the community health worker program: 196 were identified as high-risk, 103 patients were tested, and pathogenic variants were identified in 10 (9.7%), two of whom had a personal cancer history. In addition, 73 patients were tested per usual practice by a certified genetic counselor: pathogenic variants were identified in 16 (21.9%), 11 (68.8%) of whom had a personal cancer history. In the 18 months before the program, 68 patients underwent genetic testing with a certified genetic counselor, pathogenic variants were identified in 16 (23.5%), 13 (81.3%) of whom had a personal cancer history. The community health worker program led to a significant increase in testing among unaffected patients based on family history alone (odds ratio [OR] 7.0; 95% CI 3.7–13.2; P<.001), paralleled by a respective significant increase in the identification of pathogenic variants (OR 4.33; 95% CI 1.0–18.9; P=.051).

CONCLUSION:

This pilot program demonstrates the feasibility of a community health worker–supported program, using self-administered questionnaires and telehealth-based genetic services in a primarily medically underserved population. This program improved the detection of unaffected high-risk patients based on family history, increasing the volume of tests performed for this indication. Programs of this type may improve family history–based hereditary cancer testing in medically underserved patients, further enabling cancer-prevention strategies.
Large Publication Gap for Gynecologic Cancers in High–Impact Factor Journals
Authors: Sinha Nikita , McDonald Amanda , Barry Danika , Barber Emma L.
Published: August 2023

OBJECTIVE:

To analyze research publication trends in high–impact factor journals, comparing gynecologic cancers with other cancers from 2000 to 2018.

METHODS:

Abstracts from the 55 journals with the highest impact factors, as measured by Clarivate, from 2000 to 2018 were extracted from PubMed. We developed an algorithm to search the title of the abstract to determine whether the abstract was about cancer and to identify the cancer type. The algorithm was validated against the gold standard of human review in 1,143 abstracts. Article proportion was compared with site-specific incidence, mortality, and lethality from the National Cancer Institute’s Surveillance, Epidemiology and End Results database using scatterplots and nonparametric Wilcoxon signed-rank test.

RESULTS:

We identified 128,377 articles; 31,045 (24.1%) were about cancer and 1,189 (3.8%) were about gynecologic cancers. Gynecologic cancers (ovarian, cervical, and uterine) were all poorly represented in high–impact factor journals compared with their incidence, mortality, and lethality. Ovarian, uterine, and cervical cancers ranked in the bottom half of Article-to-Lethality scores (P<.01 for all comparisons). Analyses of the trends for gynecologic cancers over the past 18 years showed no change over time in Article-to-Lethality scores. Comparison of rankings by lethality with rankings by funding indicates relative underfunding of the gynecologic cancers.

CONCLUSION:

Research publications in high–impact factor journals by cancer site are not proportionate with individual cancer burden on society. Gynecologic cancers are significantly underrepresented in research publications relative to their disease burden, indicating a disparity that persists over the past 18 years. Relative underfunding of gynecologic cancers likely contributes to this publication gap.
The “Standing Peanut” Scaphoid View: A Semi-supinated Radiographic View for Intraoperative Evaluation of Screw Placement in Scaphoid Waist Fractures
Authors: Shiver A. Luke , Wallace Doyle R. , Dolan Joshua D. , Jones Keri L. , Fulcher S. Mark
Published: August 2023

Scaphoid waist fractures are the most common fracture of the scaphoid. Operative management is indicated with unstable fractures and often for nondisplaced waist fractures to decrease time to union and return to work/sport. Screw placement within the central axis of the scaphoid is paramount and correlates with outcomes. Assessment of intrascaphoid screw placement is classically done via intraoperative fluoroscopy. An additional fluoroscopic view is presented to assist in confirming implant positioning.

Along with the standard anterioposterior, lateral, pronated oblique, and “scaphoid” view we obtain a “standing peanut” view for assessment of central screw placement. This view also allows for further evaluation of center/center positioning and better assessment of fixation crossing the fracture into the proximal pole. The “standing peanut” view is best obtained in a sequential manner beginning with the forearm in neutral rotation. First, the forearm is then supinated 30 degrees; next, the wrist is placed at 45 degrees of ulnar deviation. Then finally, 10 degrees of wrist extension. We utilize this additional intraoperative view in conjunction with the standard fluoroscopic views for assessing and ensuring center-center implant positioning, particularly within the proximal pole.

When ensuring center-center positioning, we prefer this view as an adjunct view to the standard fluoroscopic views intraoperatively. It provides a beneficial view of the proximal pole delineating the number of screw threads that have obtained proximal pole purchase. We have found it particularly useful in the setting of scaphoid waist fracture nonunion with the classic ‘humpback’ deformity after correction with volar interposition grafting. Standard radiographic views may be misinterpreted regarding implant positioning if there remains any residual flexion. The view requires little in the way of training to obtain once appreciated and exposes the patient to minimal additional radiation.
The Application of Nano-drug Delivery System With Sequential Drug Release Strategies in Cancer Therapy
Authors: Li Juan , Cao Yongjing , Zhang Xiaojie , An Min , Liu Yanhua
Published: August 2023

Currently, multidrug combinations are often used clinically to improve the efficacy of oncology chemotherapy, but multidrug combinations often lead to multidrug resistance and decreased performance, resulting in more severe side effects than monotherapy. Therefore, sequential drug release strategies in time and space as well as nano-carriers that respond to the tumor microenvironment have been developed. First, the advantage of the sequential release strategy is that they can load multiple drugs simultaneously to meet their spatiotemporal requirements and stability, thus exerting synergistic effects of two or more drugs. Second, in some cases, sequential drug delivery of different molecular targets can improve the sensitivity of cancer cells to drugs. Control the metabolism of cancer cells, and remodel tumor vasculature. Finally, some drug combinations with built-in release control are used for sequential administration. This paper focuses on the use of nanotechnology and built-in control device to construct drug delivery carriers with different stimulation responses, thus achieving the sequential release of drugs. Therefore, the nano-sequential delivery carrier provides a new idea and platform for the therapeutic effect of various drugs and the synergistic effect among drugs.
Features of functional and dysfunctional CD8+ T cells to guide HIV vaccine development
Authors: Bhattacharyya Shaown , Crain Charles R. , Goldberg Benjamin , Gaiha Gaurav D.
Published: August 2023

Purpose of review

CD8+ T cell responses are a key component of the host immune response to human immunodeficiency virus (HIV) but vary significantly across individuals with distinct clinical outcomes. These differences help inform the qualitative features of HIV-specific CD8+ T cells that we should aim to induce by vaccination.

Recent findings

We review previous and more recent findings on the features of dysfunctional and functional CD8+ T cell responses that develop in individuals with uncontrolled and controlled HIV infection, with particular emphasis on proliferation, cytotoxic effector function, epitope specificity, and responses in lymph nodes. We also discuss the implications of these findings for both prophylactic and therapeutic T cell vaccine development within the context of T cell vaccine trials.

The induction of HIV specific CD8+ T cell responses is an important goal of ongoing vaccine efforts. Emerging data on the key features of CD8+ T cell responses that distinguish individuals who spontaneously control from those with progressive disease continues to provide key guidance.
Removal of an Intraosseous Venous Malformation of the Maxilla via a Transoral-transconjunctival-Transcaruncular Approach
Authors: Kamboj Alisha , Caruana Salvatore M. , Winn Bryan J.
Published: August 2023

Intraosseous vascular anomalies represent less than 1% of all bony tumors. When they involve the maxillofacial skeleton, these masses may cause substantial morbidity and aesthetic concern. Herein, we highlight a case of a maxillary intraosseous venous malformation manifesting as functional lacrimal duct obstruction with epiphora, sinus pressure, and increasing medial canthal/maxillary fullness over 2 years in a young, healthy woman. Surgical excision of the lesion was accomplished without a skin incision by coupling a transoral, midface degloving technique with a transconjunctival–transcaruncular approach. This minimally invasive technique led to complete resolution of symptoms and a satisfactory cosmetic outcome, without a cutaneous scar.
Super Selective Embolization and Immediate Resection of a High-flow Arteriovenous Malformation in the Hand
Authors: Reynoso Rafael , Echeverría Alfonso , Saldivar Rodea Carlos Alberto
Published: August 2023

A significant proportion of high-flow arteriovenous malformations (AVMs) in the hand are complex to treat due to their multicentricity, size, and risk of jeopardizing distal circulation. Therefore, AVMs are frequently considered “inoperable.” We present the case of a multifocal recurrent AVM treated in conjunction with the interventional radiology department, with intra-arterial embolization and excision followed by immediate distal revascularization to replace the resulting arterial deficit. This is a case of a 24-year-old woman with a high-flow multifocal AVM in her right hand, partially excised 2 years ago, showing a pulsatile mass in the palm and dorsum of the right hand, and a reporting pain of 8 of 10 on the visual analogue scale. The procedure was performed in our hybrid operating room. This procedure lasted 4 hours, with intraoperative bleeding of 75 mL. Three weeks after the procedure, patency and good circulation of the three revascularized fingers was demonstrated using arteriography and no evidence of vascular anomalies were found. No skin loss occurred, and no reintervention was required. For radical excision of this complex high-flow recurrent AVM, detailed intraoperative documentation of its afferent and immediate embolization with gelatin-based hemostatic agents allowed its obliteration with a low reactive material. We consider that this approach might be an option to treat AVMs that are currently considered inoperable.
A Novel No Foil-to-Skin Contact Technique for Vacuum-assisted Wound Closure in Patients with Sensitive Skin
Authors: Iliev Iliyan Emilov , Koutny-Adensamer Anna-Maria , Herbst Friedrich , Dauser Bernhard
Published: August 2023

Background:

In some patients with chronic wounds, the surrounding skin is so injured due to various underlying conditions that negative pressure dressing cannot be applied or cannot function properly. Having faced this problem in our everyday practice, we developed a new skin-sparing technique for vacuum-assisted wound closure, which ensures that the peri-wound skin does not come into contact with the transparent adhesive films.

Methods:

For 9 months (April–December 2022), we performed 32 vacuum wound dressings with the newly developed technique using the 3M ActiV.A.C. Therapy Unit and accessories, and Convatec’s VARIHESIVE, avoiding skin contact with the adhesive films.

Results:

Seven patients with 11 wounds who had sensitive skin or allergy to the conventionally used adhesive films were successfully treated with the new technique. The negative pressure wound dressings remained intact and functioned properly for up to 168 hours without compromising patients’ daily activities and therapy.

Conclusion:

The novel “no foil-to-skin contact” technique for vacuum-assisted wound closure can successfully be incorporated in the treatment of patients in whom conventional negative pressure dressings are otherwise not applicable.
Legal Ramifications of Publishing Patient Photographs: A Review of Legal Cases
Authors: Patmon Darin , Sandhu Harminder , Girotto John , Ford Ronald
Published: August 2023

Background:

The use of photography in plastic surgery has become standard of practice in recent years. Patient photographs have diverse utility and can be used to visualize medical progression, and as an educational and marketing tool. With increased publication of patient photographs outside the healthcare records, it is important to understand patient privacy rights and how they pertain to images. Additionally, it is valuable to understand the legal consequences associated with dissemination of patient photographs without proper consent.

Methods:

A retrospective analysis of the Lexis+ legal database was conducted to obtain cases that involved the improper dissemination of patient photographs or videos by surgeons. Inclusion criteria included civil cases in which the defendant was a surgeon being sued for the improper use of patient photographs. Criminal cases were excluded from analysis.

Results:

A total of 23 cases met the inclusion criteria for our study. On average, 2.13 defendants were listed per case, often including the accused surgeon and their employer. Prior photographic consent was obtained in 69.57% (n = 16) of cases. In the remaining seven cases, the defendant did not obtain consent. In all seven of these cases, either the court ruled in favor of the plaintiff or both parties reached a settlement outside court.

Conclusions:

To mitigate risk, surgeons should maintain two separate photographic consent forms for internal and external use. Additionally, a formal audit process should be established to ensure proper consent has been established before publishing patient photographs external to the electronic medical records.
USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein
Authors: Shi Songchang , Pan Xiaobin , Chen Minyong , Zhang Lihui , Zhang Shujuan , Wang Xincai , Shi Songjing , Chen Zhixin , Lin Wei , Jiang Yi
Published: August 2023

Background:

The role of thioredoxin-interacting protein (TXNIP) in lipopolysaccharide-induced liver injury in mice has been reported, but the underlying mechanisms are poorly understood.

Methods:

We overexpressed deubiquitinase in cells overexpressing TXNIP and then detected the level of TXNIP to screen out the deubiquitinase regulating TXNIP; the interaction between TXNIP and deubiquitinase was verified by coimmunoprecipitation. After knockdown of a deubiquitinase and overexpression of TXNIP in Huh7 and HepG2 cells, lipopolysaccharide was used to establish a cellular inflammatory model to explore the role of deubiquitinase and TXNIP in hepatocyte inflammation.

Results:

In this study, we discovered that ubiquitin-specific protease 5 (USP5) interacts with TXNIP and stabilizes it through deubiquitylation in Huh-7 and HepG2 cells after treatment with lipopolysaccharide. In lipopolysaccharide-treated Huh-7 and HepG2 cells, USP5 knockdown increased cell viability, reduced apoptosis, and decreased the expression of inflammatory factors, including NLRP3, IL-1β, IL-18, ASC, and procaspase-1. Overexpression of TXNIP reversed the phenotype induced by knockdown USP5.

Conclusions:

In summary, USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein.
Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Lange Marcia , Nadkarni Devika , Martin Lily , Newberry Carolyn , Kumar Sonal , Kushner Tatyana
Published: August 2023

Background and Aims:

Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD.

Methods:

MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger’s test.

Results:

Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4–52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05).

Conclusions:

There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings.
High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy
Authors: Aby Elizabeth S. , Shen Tsung-Hua , Murugappan Meena N. , Stenehjem David D. , Leventhal Thomas M.
Published: August 2023

Background and Aims:

Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States.

Methods:

Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients’ 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use.

Results:

A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively).

Conclusions:

Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention.
Behavioral weight-loss interventions for patients with NAFLD: A systematic scoping review
Authors: Balakrishnan Maya , Liu Kyle , Schmitt Sydney , Heredia Natalia I. , Sisson Amy , Montealegre Jane R. , Hernaez Ruben , Kanwal Fasiha , Foreyt John
Published: August 2023

Background:

Clinically significant weight loss—which requires sustained dietary and physical activity changes—is central to treating NAFLD. Although behavioral interventions have demonstrated effectiveness in promoting weight loss among primary prevention populations, the data are limited among patients with NAFLD who need weight loss for treatment. We undertook this scoping review to map the existing data on the characteristics, weight-loss outcomes, and determinants of success of interventions evaluated among patients with NAFLD.

Methods:

We searched Medline, EMBASE, Cochrane, PsycINFO, and Web of Science from inception to January 1, 2023 to identify publications reporting weight loss among adults with NAFLD in behavioral weight-loss interventions. We summarized interventions and classified them as successful if there was an average weight loss of ≥ 5% from baseline across enrolled participants or achieved by ≥ 50% of enrolled participants.

Results:

We included 28 studies: 10 randomized control trials, ten quasi-experimental, and 8 observational studies. Intervention delivery, duration, and counseling frequency varied; 12 were successful. Retention was highest among telephone interventions and lowest among “real-world” face-to-face interventions. Patients who were women, younger, and/or had multiple metabolic conditions were most likely to dropout. Successful interventions had biweekly counseling, specific physical activity, and calorie targets, behavioral theory grounding, and promoted goal-setting, self-monitoring, and problem-solving.

Conclusion:

There are limited data on behavioral weight-loss interventions in NAFLD. Research is needed to develop effective interventions generalizable to diverse patient populations and that maximize adherence, particularly among patients who are diabetic, women, and younger.
Discrimination between keratoconus, forme fruste keratoconus, and normal eyes using a novel OCT-based tomographer
Authors: Saad Alain , Debellemanière Guillaume , Zeboulon Pierre , Rizk Maria , Rouger Hélène , Mazharian Adrien , Grise-Dulac Alice , Panthier Christophe , Gatinel Damien
Published: August 2023

Purpose:

To combine objective machine-derived corneal parameters obtained with new swept-source optical coherence tomography (SS-OCT) tomographer (Anterion) to differentiate between normal (N), keratoconus (KC) and forme fruste KC (FFKC).

Setting:

Laser Center, Hôpital Fondation Adolphe de Rothschild, Paris, France.

Design:

Retrospective study.

Methods:

281 eyes of 281 patients were included and divided into 3 groups: N (n = 156), FFKC (n = 43), and KC (n = 82). Eyes were included in each group based on objective evaluation using Nidek Corneal Navigator, and subjective evaluation by authors. The SS-OCT system provided anterior and posterior corneal surface and pachymetry derived variables. The training set was composed of 143 eyes (95 N, 43 FFKC). Discriminant analysis was used to determine the group of an observation based on a set of variables. The obtained formula was tested in the validation set composed of 61 N and 82 KC.

Results:

Among curvature parameters, the FFKC had significantly higher irregularity index at 3 mm and 5 mm, higher inferior-superior index, higher SteepK-OppositeK index and inferiorly decentered posterior steepest keratometry. Among thickness parameters: central pachymetry, thinnest pachymetry, percentage of thickness increase from center to periphery, and inferior decentration of the thinnest point were statistically different between groups. Combination of multiple variables into a discriminant function (F1) included 5 parameters and reached an area under the receiver operating characteristic curve (AUROC) of 0.95 (sensitivity = 75%, specificity = 98.5%) for detection of FFKC. F1 differentiates N from KC with AUROC = 0.99 (sensitivity = 99%, specificity = 99%).

Conclusions:

Combining anterior and posterior curvatures variables along with pachymetric data obtained from SS-OCT allowed automated detection of early KC and KC with very good accuracy (87% and 99.5% respectively).
Intracanalicular dexamethasone insert for post–corneal crosslinking inflammation and pain: the LINK study
Authors: Nattis Alanna S. , Rosenberg Eric D. , Rasool Farhaad
Published: August 2023

Purpose:

To compare the efficacy of an intracanalicular dexamethasone insert with tapered topical steroid over 28 days after corneal cross-linking (CXL).

Setting:

Single private practice, outpatient setting.

Design:

Prospective observational randomized study.

Methods:

This prospective randomized study investigated the efficacy of a dexamethasone intracanalicular insert on post-CXL pain and inflammation in progressive keratoconus patients. 20 patients (40 eyes) were enrolled; half were randomized to the dexamethasone intracanalicular insert group; half were prescribed a 28-day topical tapering steroid regimen. All patients were evaluated for pain scores, rate of re-epithelialization, ease of the post-CXL regimen, and need for rescue pain medication after standard bilateral epithelium-off CXL on postoperative day (POD) 1, POD3, and POD4 to 7, as well as postoperative week (POW) 1, POW2, POW3, and POW4.

Results:

20 patients (40 eyes) underwent standard-of-care epithelium-off bilateral CXL for progressive keratoconus. 10 patients were randomized to receive prednisolone eyedrops on a tapering schedule after CXL; 10 patients received dexamethasone intracanalicular inserts at the time of CXL. Regardless of the postoperative steroid regimen, there was no significant difference in the rate of re-epithelialization or use of rescue pain medication between groups. There was a nominal, however, statistical difference in pain scores between groups, favoring prednisolone eyedrops. Both groups stated no difficulty in following postoperative regimens. There were no adverse events noted in relation to treatment or the CXL procedure.

Conclusions:

Using a dexamethasone insert to alleviate pain and inflammation can be considered as a safe and efficacious part of a post-CXL regimen.
Pharmacological and non-pharmacological prophylaxis in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a narrative review
Authors: Ehsan Amina
Published: August 2023

Endoscopic retrograde cholangiopancreatography is a diagnostic and therapeutic procedure for various gastrointestinal problems. Pancreatitis is a severe complication of the procedure. The main objective of this study was to address if post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented and what are the various pharmacological and non-pharmacological options along with their efficacy. Keywords “post-ERCP” and “pancreatitis” were used to search articles in Pubmed. Randomized controlled trials on patients undergoing ERCP due to any disease using pharmacological or non-pharmacological intervention published in the last 7 years were included. Observational studies, descriptive studies, reviews, and studies with no full access were excluded. The primary outcome in the trials was a frequency of post-ERCP pancreatitis. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most effective drugs in reducing the incidence of pancreatitis. The preferred route was rectal. After NSAIDs, intravenous hydration and sublingual nitrate showed promising outcomes, especially when combined with rectal NSAIDs. Other drugs like magnesium sulfate and nafamostat mesilate did reduce the incidence, but the results were not statistically significant. Epinephrine spray on duodenal papilla showed no benefits and instead had a risk of increasing the incidence. Stent placement also reduced the incidence of pancreatitis. In conclusion, rectal NSAIDs alone or combined with IV hydration and sublingual nitrate significantly reduced the incidence of pancreatitis, and stent placement was comparable to pharmacological interventions. Thus, regular use of pharmacological interventions before the procedure can help to reduce the incidence of this grave complication.
Psychological Distress in Women With Abnormal Pap Smear Results Attending Cervical Cancer Screening
Authors: Ilic Irena , Babic Goran , Dimitrijevic Aleksandra , Sipetic Grujicic Sandra , Ilic Milena
Published: August 2023

Objective

Women often experience psychological distress upon receipt of an abnormal Pap test result. This study aimed to evaluate psychological distress and its correlates among women who received an abnormal Pap screening test result.

Material and Methods

A cross-sectional study was performed in a cohort of 172 consecutive women who had attended screening for cervical cancer and who received abnormal Pap smear results and underwent additional diagnostic procedures (colposcopy/biopsy/endocervical curettage). The participants filled out a questionnaire on sociodemographic variables and the Cervical Dysplasia Distress Questionnaire. Multivariate linear regression was used for the analysis of the data. For multiple comparisons, the Bonferroni correction was applied to adjust the level of significance.

Results

In women who received an abnormal Pap smear result, the independent correlate of higher psychological distress (by Cervical Dysplasia Distress Questionnaire score) before diagnostic procedures was lower satisfaction with information/support received from other people (p = .002). Correlates of psychological distress in women older than 40 years with abnormal Pap smear were anxiety (p = .042) and worry about having cervical cancer, general health and having sex (p = .044).

Conclusions

The authors’ findings could enable control of factors predictive of psychological distress in women who received a positive Pap smear screening test before undergoing diagnostic procedures, primarily via active provision of targeted information.
Translating Knowledge Into Clinical Practice
Authors: Mitrea Nicoleta , Brown Britny , Charpentier Maggie , Mullalli Henri Andreas , Laska Irena , Sinani Anila , Banu Reghina , Paice Judith A. , Ancuta Camelia
Published: August 2023

For learning to influence change in palliative clinical practice, education needs to be ongoing, incorporating specific interventions targeted to the learner, in a format that enhances knowledge and networking. This novel, online, interactive, case-based educational offering provided a method to allow ongoing integration of palliative care principles for health care professionals who attended the End-of-Life Nursing Education Consortium/Open Medical Institute courses in Salzburg during 2019-2022. Eight monthly teleconferences based on challenging clinical cases allowed discussion between palliative care professionals from 9 countries, serving as a mechanism for deepening theoretical information, allowing incorporation of best practice into the clinical setting, and, ultimately, improving care for all with serious illness. Many of the challenges encountered providing palliative care are universal. Through case vignettes, the group has been able to offer specific interventions, advances in practice, and discussions of approaches toward family and other health care professionals to provide optimal care. The participants report that the opportunity to learn from and support peers in other countries has been a rewarding and emotionally uplifting experience. These discussions were highly rated by participants who strongly voiced that the interactions would change their clinical practice to positively impact patient care.
Evolution of statistical models for meta-analysis and implications for best practice
Authors: Kelley George A. , Kelley Kristi S.
Published: August 2023

Purpose of review

Meta-analyses are a common and important component of clinical practice guidelines. Concomitantly, there has been a tremendous increase over the past three decades in the number of published meta-analyses. An important factor in the quality of the results from a meta-analysis rests on selecting the most appropriate pooling model. In this brief review, the evolution of the numerous different pooling models that extend beyond the traditional fixed effect, fixed effects, and random effects models is described, with a focus on estimating between-study variance, that is, heterogeneity. The most recent evidence, including alternative models, is also described and recommendations for model selection and reporting provided.

Recent findings

In the absence of checking for between-study normality, appropriately conducted simulation studies have found that the IVhet model, a quasi-likelihood approach, may be the best model for pooling results in an aggregate data meta-analysis.

The IVhet model is recommended for pooling results for an aggregate data meta-analysis. If there is insistence on a random effects model, the restricted maximum likelihood method along with the Knapp-Hartung adjustment is recommended. A need exists for a large, collaborative, appropriately conducted simulation study that examines which pooling models are best based on the scenario presented.
Antibody neutralization capacity after COVID-19 vaccination in people with HIV (CIHR Canadian HIV trials network 328)
Authors: Costiniuk Cecilia T. , Singer Joel , Lee Terry , Galipeau Yannick , McCluskie Pauline S. , Arnold Corey , Langlois Marc-André , Needham Judy , Jenabian Mohammad-Ali , Burchell Ann N. , Samji Hasina , Chambers Catharine , Walmsley Sharon , Ostrowski Mario , Kovacs Colin , Tan Darrell H.S. , Harris Marianne , Hull Mark , Brumme Zabrina L. , Lapointe Hope R. , Brockman Mark A. , Margolese Shari , Mandarino Enrico , Samarani Suzanne , Vulesevic Branka , Lebouche Bertrand , Angel Jonathan B. , Routy Jean-Pierre , Cooper Curtis L. , Anis Aslam H.
Published: August 2023

Objectives:

Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Here, we compare COVID-19 vaccine-induced antibody neutralization capacity in PLWH vs. HIV-negative individuals following two vaccine doses.

Design:

In Canadian prospective observational cohorts, inlcuding a multi-centre study of PLWH receiving ≥2 COVID-19 vaccinations (mRNA or ChAdOx1-S), and a parallel study of HIV-negative controls (Stop the Spread Ottawa Cohort), we measured vaccine-induced neutralization capacity 3 months post-dose 2 (± 1 month).

Methods:

COVID-19 neutralization efficiency was measured by calculating the half maximal inhibitory dilution(ID50) using a high-throughput protein based neutralization assay for Ancestral(Wuhan), Delta and Omicron (BA.1) spike variants. Univariable and multivariable quantile regression were used to compareCOVID-19-specific antibody neutralization capacity by HIV status.

Results:

Neutralization assays were performed on 256 PLWH and 256 controls based on specimen availability at the timepoint of interest, having received 2 vaccines and known date of vaccination. There was a significant interaction between HIV status and previous COVID-19 infection status in median ID50. There were no differences in median ID50 for HIV+ vs HIV-negative persons without past COVID-19 infection.For participants with past COVID-19 infection, median ICD50 was significantly higher in controls than in PLWH for Ancestral SARS-CoV-2 and Omicron variants, with a trend for the Delta variant in the same direction.

Conclusion:

Vaccine-induced SARS-CoV-2 neutralization capacity was similar between PLWH vs HIV-negative persons without past COVID-19 infection, demonstrating favourable humoral-mediated immunogenicity. Both HIV+ and HIV-negative persons demonstrated hybrid immunity.

Funding:

Public Health Agency of Canada, through the Vaccine Surveillance Reference group, the COVID-19 Immunity Task Force (2122-HQ-000075) and the CTN. Production of COVID-19 reagents was financially supported by National Research Council of Canada (NRC) Pandemic Response Challenge Program.

Trial registration:

clinicaltrials.gov NCT04894448
The Proportional Relationship Among the Aesthetic Units of the Upper Lip: A 3-Dimensional Morphological Analysis of Young Adults
Authors: Sun Weiyi , Xu Meng , Song Tao
Published: August 2023

A deep understanding of the proportional relationship among the crucial aesthetic units of the upper lip is essential for lip treatment procedures, yet limited information can be found. The authors used 3-dimensional (D) photogrammetry to analyze the proportional features involving different lip structures. One hundred sixty volunteers (aged 18–35 y) were included, and standardized frontal view 3D images were obtained. A series of anthropometric parameters were measured, including linear, angular, and ratio parameters. The authors took the philtrum as one structure of particular concern. The philtrum was classified into 4 groups according to the shape of philtral columns, and philtrum depth was measured. The authors analyzed the correlations between the philtrum and the vermillion lip. They found significant differences in philtrum depth among different type groups. A significant negative correlation between philtral depth and philtrum length was found, which indicated that a long philtrum was more likely to be accompanied by a flat philtrum with shallow depth. The philtrum width was significantly correlated with the mouth width with a mean ratio of 0.25. The authors also found a significantly negative correlation between philtral depth and angle of Cupid’s bow’s peak (Achp), and a positive correlation between Achp and mouth width. This study used 3D photography to quantitatively analyze proportional characteristics among labial aesthetic units in young Chinese adults. The results showed that the philtrum and the vermillion lip morphology were closely related, providing helpful references in perioral procedures.
Pantoea leporis sp. nov., isolated from the faecal material of a rabbit
Authors: Kerin Lindsay , Lawson Paul A. , Dutton Nicole , Bevis Durward L. , McLaughlin Richard
Published: August 2023

A facultative anaerobic, Gram-stain-negative rod-shaped bacterium, designated RT, was isolated from the faecal material of a rabbit (Sylvilagus floridanus). The strain could not be identified using an MALDI Biotyper sirius CA System. The closest matches based on the Bruker library were members of the genera

Citrobacter

and

Pantoea

. However, the score value was in the range of no organism identification possible. Based on pairwise of 16S rRNA gene sequence analysis, the isolate was found to be a member of the family

Erwiniaceae

. The highest sequence similarities were found to the sequences of

Pantoea rodasii

LMG 26273T (98.7 %),

Leclercia adecarboxylata

NBRC 102595T (98.5 %) and

Enterobacter huaxiensis

090008T (98.4 %). Phylogenetic and whole genome analysis demonstrated that strain RT represents a novel species within the genus

Pantoea

. The predominant cellular fatty acids of strain RT were C16 : 0 and products present in summed feature 2 (C12 : 0) aldehyde, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). In silico genome analysis showed the presence of enzymes required for production of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylserine. The G+C content determined from the genome was 54.94 mol %. Based on biochemical, phylogenetic, genotypic and chemotaxonomic criteria, the isolate represents a novel species of the genus

Pantoea

for which the name Pantoea leporis sp. nov. is proposed. The type strain is strain RT (=CCUG 76269T=ATCC TSD-291T).
A mechanical modelling framework to study endothelial permeability
Authors: Keshavanarayana Pradeep , Spill Fabian
Published: August 2023

The inner lining of blood vessels, the endothelium, is made up of endothelial cells. Vascular endothelial (VE)-cadherin protein forms a bond with VE-cadherin from neighbouring cells (homophilic bond) to determine the size of gaps between the cells and thereby regulate the size of particles that can cross the endothelium. Chemical cues such as Thrombin, along with mechanical properties of the cell and extracellular matrix (ECM) are known to affect the permeability of endothelial cells. Abnormal permeability is found in patients suffering from diseases including cardiovascular diseases, cancer, and COVID-19. Even though some of the regulatory mechanisms affecting endothelial permeability are well studied, details of how several mechanical and chemical stimuli acting simultaneously affect endothelial permeability are not yet understood.

In this article, we present a continuum-level mechanical modelling framework to study the highly dynamic nature of the VE-cadherin bonds. Taking inspiration from the catch-slip behaviour that VE-cadherin complexes are known to exhibit, we model VE-cadherin homophilic bond as cohesive contact with damage following a traction-separation law. We explicitly model the actin-cytoskeleton, and substrate to study their role in permeability. Our studies show that mechano-chemical coupling is necessary to simulate the influence of the mechanical properties of the substrate on permeability. Simulations show that shear between cells is responsible for the variation in permeability between bi-cellular and tri-cellular junctions, explaining the phenotypic differences observed in experiments. An increase in the magnitude of traction force that endothelial cells experience results in increased permeability, and it is found that the effect is higher on stiffer ECM. Finally, we show that the cylindrical monolayer exhibits higher permeability than the planar monolayer under unconstrained cases. Thus, we present a contact mechanics-based mechano-chemical model to investigate the variation in permeability of endothelial monolayer due to multiple loads acting simultaneously.
Device measured sedentary behaviour, sleep, light and moderate-vigorous physical activity and cardio-metabolic health: A compositional individual participant data analysis in the ProPASS consortium
Authors: Blodgett JM , Ahmadi MN , Atkin AJ , Chastin S , Chan HW , Suorsa K , Bakker EA , Hettiarcachchi P , Johansson PJ , Sherar LB , Rangul V , Pulsford RM , Mishra G , Eijsvogel TMH , Stenholm S , Hughes AD , Teixeira-Pinto AM , Eklund U , Lee IM ,   ProPASS collaboration, Holtermann A , Koster A , Stamatakis E , Hamer M
Published: August 2023

Background/Aims

Physical inactivity, sedentary behaviour (SB) and inadequate sleep are key behavioural risk factors of cardiometabolic diseases; each is mainly considered in isolation. The study aim was to investigate associations of five movement behaviour compositions with adiposity and cardiometabolic biomarkers.

Methods

Cross-sectional data from 15,246 participants from the Prospective Physical Activity, Sitting and Sleep consortium (ProPASS) were analysed. Time spent in sleep, SB, standing, light-intensity physical activity (LIPA) and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included BMI, waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides and HbA1c. Compositional linear regression examined associations between compositions and each outcome, including modelling reallocation of time between behaviours.

Results

The average daily composition of the sample(age:53.7±9.7years; 54.7%female) was 7.7hrs sleeping,10.4hrs sedentary,3.1hrs standing,1.5hrs LIPA and 1.3hrs MVPA. A greater proportion of MVPA time and smaller proportion of SB time was associated with better outcomes. Reallocating time from SB,standing,LIPA or sleep into MVPA had the largest theoretical improvement across all outcomes. For example, replacing 30min of SB, sleep, standing or LIPA with MVPA was associated with -0.63 (95%CI -0.48,-0.79), -0.43 (-0.25,-0.59), -0.40 (-0.25,-0.56) and -0.15 (0.05,-0.34)kg/m2lower BMI, respectively. A larger proportion of standing time was beneficial for outcomes; sleep had a detrimental association when replacing LIPA or MVPA and positive association when replacing SB. The minimal displacement into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day.

Conclusions

Compositional data analyses revealed a distinct hierarchy of behaviours. MVPA demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing or LIPA required substantial changes in daily activity.
ADAR2 inhibits ER-targeted mRNA translation via regulating nucleolar assembly of signal recognition particle
Authors: Feng Rui , Wang Yuci , Ran Dongmei , Li Ying , Zhou Hui , Liu Qi , Zhang Yingchun , Ma Honghui , Chen Hao
Published: August 2023

Adenosine-to-inosine RNA editing is mediated by ADAR family proteins and plays critical roles in regulating gene expression. Unlike other ADAR family members, ADAR2 mostly resides in nucleolus. The exact roles of this peculiar cellular distribution of ADAR2 is still largely unknown. Here, our current study unexpectedly uncovered that nucleoli-localized ADAR2 is involved in negatively regulating ER-targeted mRNA translation, which is mediated by SRP. Importantly, this regulation is not archived through direct binding of mRNA by ADAR2 or dependent on A-to-I editing of 7SL RNA. Further analysis indicated that ADAR2 directly interacts with SRP protein components, especially SRP68, in a RNA-independent manner and probably represses the SRP assembly. Hence, we proved insights into the novel functions of ADAR2 and long-lasting enigma about the peculiar translocation of SRP proteins into nucleoli during SRP biogenesis.
The structural basis for deubiquitination by the fingerless USP-type effector TssM
Authors: Hermanns Thomas , Uthoff Matthias , Baumann Ulrich , Hofmann Kay
Published: August 2023

Intracellular bacteria are threatened by ubiquitin-mediated autophagy, whenever the bacterial surface or enclosing membrane structures become targets of host ubiquitin ligases. As a countermeasure, many intracellular pathogens encode deubiquitinase (DUB) effectors to keep their surfaces free of ubiquitin modifications. Most bacterial DUBs belong to the OTU or CE-clan families. The betaproteobacteriaB. pseudomalleiandB. mallei, causative agents of melioidosis and glanders, respectively, encode the TssM effector, the only known bacterial DUB belonging to the USP class. TssM is much shorter than typical eukaryotic USP enzymes and lacks the canonical ubiquitin-recognition region. By solving the crystal structures of isolated TssM and its complex with ubiquitin, we found that TssM lacks the entire ‘Fingers’ subdomain of the USP fold. Instead, the TssM family has evolved the functionally analog ‘Littlefinger’ loop, which is located towards the end of the USP domain and recognizes different ubiquitin interfaces than those used by canonical USPs. The structures also revealed the presence of an N-terminal immunoglobulin-fold domain, which is able to form a strand-exchange dimer and might mediate TssM localization to the bacterial surface.