bluuebunny/crossref_metadata_2025 huggingface dataset:
SpliceTools, a suite of downstream RNA splicing analysis tools to investigate mechanisms and impact of alternative splicing
Authors: Flemington Erik K , Flemington Samuel A , O’Grady Tina M , Baddoo Melody , Nguyen Trang , Dong Yan , Ungerleider Nathan A
Published: March 2023

As a fundamental aspect of normal cell signaling and disease states, there is great interest in determining alternative splicing (AS) changes in physiologic, pathologic, and pharmacologic settings. High throughput RNA sequencing and specialized software to detect AS has greatly enhanced our ability to determine transcriptome-wide splicing changes. Despite the richness of this data, deriving meaning from sometimes thousands of AS events is a substantial bottleneck for most investigators. We present SpliceTools, a suite of data processing modules that arms investigators with the ability to quickly produce summary statistics, mechanistic insights, and functional significance of AS changes through command line or through an online user interface. Utilizing RNA-seq datasets for 186 RNA binding protein knockdowns, nonsense mediated RNA decay inhibition, and pharmacologic splicing inhibition, we illustrate the utility of SpliceTools to distinguish splicing disruption from regulated transcript isoform changes, we show the broad transcriptome footprint of the pharmacologic splicing inhibitor, indisulam, we illustrate the utility in uncovering mechanistic underpinnings of splicing inhibition, we identify predicted neo-epitopes in pharmacologic splicing inhibition, and we show the impact of splicing alterations induced by indisulam on cell cycle progression. Together, SpliceTools puts rapid and easy downstream analysis at the fingertips of any investigator studying AS.
Proximal binding of dCas9 at a DNA double strand break stimulates homology-directed repair as a local inhibitor of classical non-homologous end joining
Authors: Feng Yi-Li , Liu Si-Cheng , Chen Ruo-Dan , Sun Xiu-Na , Xiao Jing-Jing , Xiang Ji-Feng , Xie An-Yong
Published: March 2023

In CRISPR/Cas9 genome editing, the tight and persistent target binding of Cas9 provides an opportunity for efficient genetic and epigenetic modification on genome. In particular, technologies based on catalytically dead Cas9 (dCas9) have been developed to enable genomic regulation and live imaging in a site-specific manner. While post-cleavage target residence of CRISPR/Cas9 could alter the pathway choice in repair of Cas9-induced DNA double strand breaks (DSBs), it is possible that dCas9 residing adjacent to a break may also determine the repair pathway for this DSB, providing an opportunity to control genome editing. Here, we found that loading dCas9 onto a DSB-adjacent site stimulated homology-directed repair (HDR) of this DSB by locally blocking recruitment of classical non-homologous end-joining (c-NHEJ) factors and suppressing c-NHEJ in mammalian cells. We further repurposed dCas9 proximal binding to increase HDR-mediated CRISPR genome editing by up to 4-fold while avoiding exacerbation of off-target effects. This dCas9-based local inhibitor provided a novel strategy of c-NHEJ inhibition in CRISPR genome editing in place of small molecule c-NHEJ inhibitors, which are often used to increase HDR-mediated genome editing but undesirably exacerbate off-target effects.
Variable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay
Authors: Danziger Natalie , Sokol Ethan S , Graf Ryon P , Hiemenz Matthew C , Maule Jake , Parimi Vamsi , Palmieri Carlo , Pusztai Lajos , Ross Jeffrey S , Huang Richard S P
Published: March 2023

Background

In 2020, pembrolizumab was approved as a therapy for triple-negative breast cancer (TNBC) with the companion diagnostic DAKO 22C3 programmed death ligand-1 (PD-L1) immunohistochemistry assay. The study aimed to determine the landscape of PD-L1 expression as detected by the DAKO 22C3 PD-L1 assay in breast cancer subtypes and compare the clinicopathologic and genomic characteristics of PD-L1 positive and negative TNBC.

Methods

PD-L1 expression using the DAKO 22C3 antibody was scored using a combined positive score (CPS) and positive status was defined as CPS ≥10. Comprehensive genomic profiling was performed using the FoundationOne CDx assay.

Results

Of the 396 BC patients stained with DAKO 22C3, the majority were HR+/HER2− and TNBC (42% and 36%, respectively). Median PD-L1 expression and frequency of CPS ≥10 was highest in TNBC cases (median: 7.5, 50% CPS ≥10) and lowest in the HR+/HER2− group (median: 1.0, 15.5% CPS ≥10) (P < .0001). A comparison of PD-L1 positive and PD-L1 negative TNBC demonstrated no significant differences in clinicopathologic or genomic characteristics. TNBC tissue samples from the breast did have an observed enrichment for PD-L1 positivity compared to TNBC tissue samples from a metastatic site (57% vs. 44%), but this was not statistically significant (P = .1766). In the HR+/HER2− group, genomic alterations in TP53, CREBBP, and CCNE1 were more prevalent and genomic loss of heterozygosity was higher in the PD-L1(+) group compared to the PD-L1(−) group.

Conclusions

The subtypes of breast cancer have distinct patterns of PD-L1 expression, supporting that further research of immunotherapies may include specific evaluation of optimum cutoffs for non-TNBC patients. In TNBC, PD-L1 positivity is not associated with other clinicopathologic or genomic features and should be integrated into future studies of immunotherapy efficacy.
Pion–nucleon sigma term σπNand deeply bound pionic atoms
Authors: Ikeno Natsumi , Nishi Takahiro , Itahashi Kenta , Nose-Togawa Naoko , Tani Akari , Hirenzaki Satoru
Published: March 2023

We investigate the possibility of determining the value of the pion–nucleon sigma term σπN precisely by the experimental observables of deeply bound pionic atoms. We discuss the sensitivity of the observables to σπN and take into account the typical errors of up-to-date experiments on deeply bound pionic atoms. We find that the gap in the binding energies and the width of the deeply bound pionic states are good observables for σπN value determination with experimental data. We also discuss the expected difficulties for the accurate determination of the value of σπN due to the correlation between the σ term and the potential parameter in the pion–nucleus optical potential.
A randomized, double-blind, placebo-controlled, parallel group study on the effects of a cathepsin S inhibitor in primary Sjögren’s syndrome
Authors: Bentley Darren , Fisher Benjamin A , Barone Francesca , Kolb Fabrice A , Attley Gemma
Published: March 2023

Objectives

Primary SS (pSS) is a chronic autoimmune disorder characterized by mucosal dryness and systemic symptoms. We tested the effects of inhibition of cathepsin S using the potent and selective inhibitor RO5459072 on disease activity and symptoms of pSS.

Methods

This was a randomized, double-blind, placebo-controlled, parallel-group, Phase IIA study to investigate the effects of RO5459072 (100 mg twice daily; 200 mg per day). Seventy-five patients with pSS were randomized 1:1 to receive either RO5459072 or placebo for 12 weeks. The primary outcome was the proportion of patients with a ≥3 point reduction from baseline in EULAR SS Disease Activity Index (ESSDAI) score. We also investigated the effects of RO5459072 on quality of life, exocrine gland function, biomarkers related to SS, and safety and tolerability.

Results

The proportion of patients showing an improvement in ESSDAI score was not significantly different between the RO5459072 and placebo arms. No clinically meaningful treatment effects were observed in favour of RO5459072 for all secondary outcomes. Analysis of soluble biomarkers indicated target engagement between RO5459072 and cathepsin S. There were modest decreases in the number of circulating B cells and T cells in the RO5459072 group, although these did not reach significance. RO5459072 was safe and well-tolerated.

Conclusions

There was no clinically relevant improvement in ESSDAI score (primary endpoint), and no apparent benefit in favour of RO5459072 in any of the secondary clinical endpoints. Further work is needed in order to understand the mechanisms of MHC-II-mediated immune stimulation in pSS.

Trial registration

ClinicalTrials.gov; NCT02701985.
“Spin” among abstracts of randomized controlled trials in sleep medicine: a research-on-research study
Authors: Guo Feiyang , Zhao Tingting , Zhai Qianglan , Fang Xiaolin , Yue Haoze , Hua Fang , He Hong
Published: March 2023

Study Objectives

“Spin,” using reporting strategies to distort study results, can mislead readers of medical research. This study aimed to evaluate the prevalence and characteristics of “spin” among randomized controlled trial (RCT) abstracts published in sleep medicine journals, and to identify factors associated with its presence and severity.

Methods

The search for RCTs published between 2010 and 2020 were conducted in seven reputable journals of sleep medicine. Abstracts of RCTs with statistically nonsignificant primary outcomes were included and analyzed for “spin,” according to predetermined “spin” strategies. Chi-square tests or logistic regression analyses were performed to detect the association between characteristics of included abstracts and the presence and severity of “spin.”

Results

A total of 114 RCT abstracts were included in this study, of which 89 (78.1%) were identified as having at least one type of “spin” strategy. Sixty-six abstracts (57.9%) had “spin” in the Results section, 82 (71.9%) abstracts presented with “spin” in the Conclusions section. The presence of “spin” varied significantly among RCTs based on the different categories of research area (p = 0.047) and the statistician involvement (p = 0.045). Furthermore, research area (p = 0.019) and funding status (p = 0.033) were significant factors associated with the severity of “spin.”

Conclusions

The prevalence of “spin” is high among RCT abstracts in sleep medicine. This raises the need for researchers, editors, and other stakeholders to be aware of the issue of “spin” and make joint efforts to eliminate it in future publications.
Deep Brain Stimulation for Substance Use Disorders? An Exploratory Qualitative Study of Perspectives of People Currently in Treatment
Authors: Versalovic Erika , Klein Eran , Goering Sara , Ngo Quyen , Gliske Kate , Boulicault Marion , Sullivan Laura Specker , Thomas Mark J. , Widge Alik S.
Published: March 2023

Objective

Although previous studies have discussed the promise of deep brain stimulation (DBS) as a possible treatment for substance use disorders (SUDs) and collected researcher perspectives on possible ethical issues surrounding it, none have consulted people with SUDs themselves. We addressed this gap by interviewing people with SUDs.

Methods

Participants viewed a short video introducing DBS, followed by a 1.5-hour semistructured interview on their experiences with SUDs and their perspective on DBS as a possible treatment option. Interviews were analyzed by multiple coders who iteratively identified salient themes.

Results

We interviewed 20 people in 12-step–based, inpatient treatment programs (10 [50%] White/Caucasian, 7 Black/African American [35%], 2 Asian [10%], 1 Hispanic/Latino [5%], and 1 [5%] Alaska Native/American Indian; 9 women [45%], 11 men [55%]). Interviewees described a variety of barriers they currently faced through the course of their disease that mirrored barriers often associated with DBS (stigma, invasiveness, maintenance burdens, privacy risks) and thus made them more open to the possibility of DBS as a future treatment option.

Conclusions

Individuals with SUDs gave relatively less weight to surgical risks and clinical burdens associated with DBS than previous surveys of provider attitudes anticipated. These differences derived largely from their experiences living with an often-fatal disease and encountering limitations of current treatment options. These findings support the study of DBS as a treatment option for SUDs, with extensive input from people with SUDs and advocates.
Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient
Authors: Erdoes Gabor , Faraoni David , Koster Andreas , Steiner Marie E. , Ghadimi Kamrouz , Levy Jerrold H.
Published: March 2023

Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.
Antiphospholipid syndrome management: a 2023 update and practical algorithm-based approach
Authors: Ambati Amala , Knight Jason S. , Zuo Yu
Published: March 2023

Purpose of review

Antiphospholipid syndrome (APS) is an acquired thrombo-inflammatory disease that has morbid and sometimes devastating effects on patients and their families. This review will discuss the most recent international societal treatment guidelines and propose practical management algorithms for various APS sub-types.

Recent findings

APS represents a disease spectrum. Although thrombosis and pregnancy morbidities are traditional hallmarks of APS, a variety of extra-criteria clinical phenotypes can often be seen, which makes clinical management more challenging. Primary APS thrombosis prophylaxis should take a risk-stratified approach. Although vitamin K antagonists (VKAs) or heparin/low molecular weight heparin (LMWH) remain the preferred treatment for secondary APS thrombosis prophylaxis, some international society guidelines support the use of direct oral anticoagulants (DOACs) in certain circumstances. Careful monitoring and individualized obstetric care with the use of aspirin and heparin/LMWH will improve pregnancy outcomes among pregnant individuals with APS. Treatment of microvascular and catastrophic APS remains challenging. While the addition of various immunosuppressive agents is often utilized, further systemic evaluations of their use are warranted before definitive recommendations can be made. Several new therapeutic strategies are on the horizon that might enable more personalized and targeted APS management in the near future.

Although the knowledge of APS pathogenesis has grown in recent years, the management principles and strategies are largely unchanged. There is an unmet need for evaluating pharmacological agents, beyond anticoagulants, that target diverse thromboinflammatory pathways.
Epidemiology of Lumbar Spine Conditions in Professional Baseball Players
Authors: Makhni Melvin C. , Curriero Frank C. , Yeung Caleb M. , Kvit Anton , Ahmad Christopher S. , Lehman Ronald A.
Published: March 2023

Study Design:

A retrospective case series study.

Objective:

To analyze the epidemiology and burden of diagnoses of lumbar spinal conditions affecting Major League Baseball (MLB) and Minor League Baseball players.

Summary of Background Data:

Lumbar spinal conditions are a common cause of low back pain in the general population and can be caused by participation in sports and athletics. Data concerning the epidemiology of these injuries in professional baseball players are limited.

Methods:

We collected deidentified MLB and Minor League Baseball data concerning lumbar spine conditions (lumbar disk herniations, lumbar degenerative disease, or pars conditions) from 2011 to 2017 using the MLB-commissioned Health and Injury Tracking System database. Data concerning days missed because of injury, need for surgery, and player participation and career-ending status were assessed. Injury rates were reported as injuries per 1000 athlete exposures in concordance with prior studies.

Results:

Over 2011–2017, 5948 days of play were missed because of 206 lumbar spine-related injuries, of which 60 (29.1%) were season ending. Twenty-seven (13.1%) of these injuries required surgery. The most common injury among both pitchers and position players were lumbar disk herniations (45, 44.1% and 41, 39.4%, respectively). More surgeries were performed for lumbar disk herniations and degenerative disk disease compared with pars conditions (74% and 18.5% vs. 3.7%). Injury rates for pitchers was significantly higher than those of other position players 0.111 per 1000 AEs versus 0.040 per 1000 AEs (P<0.0001). Injuries requiring surgery did not vary significantly by league, age group, or player position.

Conclusions:

Lumbar spine-related injuries incurred substantial disability and days missed from play in professional baseball players. Lumbar disk herniations were the most common injury, and together with pars conditions led to higher rates of surgery compared with degenerative conditions.

Level of Evidence:

III
Clinical response under MEK inhibitor alone in metastatic melanoma with a novel fusion involving the RAF1 gene
Authors: Boileau Marie , Descarpentries Clotilde , Delzenne Guillaume , Trentesaux Victorine , Greliak Anna , Jamme Philippe , Marchetti Philippe , Mortier Laurent
Published: March 2023

Currently, in the absence of BRAFV600 mutation, the management of advanced melanomas is based on immunotherapies, but only half of the patients are responders. RAF1 (also named CRAF) fusions occur in 1–2.1% of wild-type melanomas. Preclinical data suggest that the presence of RAF fusion may be sensitive to MEK inhibitors. We report the case of a patient with an advanced melanoma harboring an EFCC1–RAF1 fusion who showed a clinical benefit from and a partial response to a MEK inhibitor.
A Streamlined Algorithmic Process for Creating Three-dimensional Printed Forearm Casts
Authors: Alshawaf Solaiman M. , Burhamah Waleed , Alwazzan Sabika , AlYouha Sarah
Published: March 2023

Three-dimensional (3D) printing is a rapidly evolving field that has found its way into the medical field, providing unsurpassed contributions to the provision of patient-centered care. Its utilization lies in optimizing preoperative planning, the creation and customization of surgical guides and implants, and the designing of models that can be used to augment patient counseling and education. We integrate a simple yet effective method of scanning the forearm using an iPad device with Xkelet software to obtain a 3D printable stereolithography file, which is then incorporated to our suggested algorithmic model for designing a 3D cast, utilizing Rhinocerus design software and Grasshopper plugin. The algorithm implements a stepwise process of retopologizing the mesh, division of the cast model, creating the base surface, applying proper clearance and thickness to the mold, and creating a lightweight structure through the addition of ventilation holes to the surface with a joint connector between the two plates. In our experience, scanning and design of the patient-specific forearm cast using Xkelet and Rhinocerus, alongside implementing an algorithmic model through Grasshopper plugin has dramatically reduced the designing process from 2 to 3 hours to 4–10 minutes, further increasing the number of patient scans that can be sequenced in a short duration. In this article, we introduce a streamlined algorithmic process for the use of 3D scanning and processing software to create forearm casts that are tailored to the patients’ dimensions. We emphasize the implementation of computer-aided design software for a quicker and more accurate design process.
Hemodynamic Gain Index Is Associated With Cardiovascular Mortality and Improves Risk Prediction
Authors: Laukkanen Jari A. , Isiozor Nzechukwu M. , Willeit Peter , Kunutsor Setor K.
Published: March 2023

Purpose:

The hemodynamic gain index (HGI) and cardiorespiratory fitness (CRF) are parameters assessed during cardiopulmonary exercise testing (CPX). The association between the HGI and cardiovascular disease (CVD) mortality is uncertain. We evaluated the association between the HGI and CVD mortality risk using a prospective study.

Methods:

The HGI was calculated using heart rate (HR) and systolic blood pressure (SBP) measured in 1634 men aged 42-61 yr during CPX, using the formula: [(HRpeak× SBPpeak) − (HRrest × SBPrest)]/(HRrest × SBPrest). Cardiorespiratory fitness was directly measured using a respiratory gas exchange analyzer.

Results:

During a median (IQR) follow-up of 28.7 (19.0, 31.4) yr, 439 CVD deaths occurred. The risk of CVD mortality decreased continuously with the increasing HGI (P value for nonlinearity = .28). Each unit higher HGI (1.06 bpm/mm Hg) was associated with a decreased risk of CVD mortality (HR = 0.80: 95% CI, 0.71-0.89), which was attenuated after further adjustment for CRF (HR = 0.92: 95% CI, 0.81-1.04). Cardiorespiratory fitness was associated with CVD mortality and the association remained after adjustment for the HGI: (HR = 0.86: 95% CI, 0.80-0.92) per each unit (MET) higher CRF. Addition of the HGI to a CVD mortality risk prediction model improved risk discrimination (C-index change = 0.0285; P < .001) and reclassification (net reclassification improvement = 8.34%; P < .001). The corresponding values for CRF were a C-index change of 0.0413 (P < .001) and a categorical net reclassification improvement of 14.74% (P < .001).

Conclusions:

The higher HGI is inversely associated with CVD mortality in a graded fashion, but the association is partly dependent on CRF levels. The HGI improves the prediction and reclassification of the risk for CVD mortality.
Decision taking in corneal refractive surgery
Authors: Nuijts Rudy M.M.A. , Cummings Arthur B. , Dick H. Burkhard , Taneri Suphi , Vinciguerra Paolo , Cochener-Lamard Béatrice , Lapid-Gortzak Ruth , Kanellopoulos A. John , Agarwal Kanika , Karadimou Despoina , Konstantinidou Elena , Shetty Rohit , Khamar Pooja , Ambrósio Renato , Machado Aydano P , Marcelo Lyra João
Published: March 2023

A 27-year-old woman who wants to get rid of contact lenses and spectacles was seen at our clinic. She had strabismus surgery as a child and was patched for the right eye but now shows mild nondisturbing exophoria. Infrequently, she likes to box in the sports school.

Her corrected distance visual acuity at presentation in the right eye was 20/16 with −3.75 −0.75 × 50 and in the left eye 20/16 with −3.75 −1.25 × 142. Her cycloplegic refraction in the right eye was −3.75 −0.75 × 44 and in the left eye was −3.25 −1.25 × 147. The left eye is the dominant eye. The tear break-up time was 8 seconds in both eyes, and the Schirmer tear test was 7 to 10 mm in right and left eyes, respectively. Pupil sizes under mesopic conditions were 6.62 mm and 6.68 mm.

The anterior chamber depth (ACD) (measured from the epithelium) in the right eye was 3.89 mm and in the left eye was 3.87 mm. The corneal thickness was 503 μm and 493 μm of the right and left eye, respectively. Corneal endothelial cell density was on average 2700 cells/mm2for both eyes. Slitlamp biomicroscopy showed clear corneas and a normal flat iris configuration. Supplemental Figures 1 to 4 (available at http://links.lww.com/JRS/A818, http://links.lww.com/JRS/A819, http://links.lww.com/JRS/A820, and http://links.lww.com/JRS/A821) show the corneal topography and Belin-Ambrósio deviation (BAD) maps at presentation of the right eye and left eye, respectively.

Would you consider this patient a candidate for corneal refractive surgery (eg, laser-assisted subepithelial keratectomy, laser in situ keratomileusis [LASIK], or small-incision lenticule extraction [SMILE] procedure)? Has your opinion changed given the recent opinion of the U.S. Food and Drug Administration (FDA) regarding LASIK?1The patient herself is slightly favoring an implantation of a phakic intraocular lens (pIOL), as she prefers something reversible. Would you implant a pIOL, and which type of IOL, for this level of myopia?

What is your diagnosis or are additional diagnostic methodologies needed to establish a diagnosis? What is your treatment advice for this patient?

REFERENCES

1. U.S. Food and Drug Administration, HHS. Laser-assisted in situ keratomileusis (LASIK) lasers–patient labeling recommendations; draft guidance for industry and food and drug administration staff; availability. July 28, 2022, Federal Register; 87 FR 45334. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/laser-assisted-situ-keratomileusis-lasik-lasers-patient-labeling-recommendations Accessed January 25, 2023
The Grip on Health Intervention to Prevent Health Problems Among Workers With a Lower Socioeconomic Position
Authors: Schaap Rosanne , Schaafsma Frederieke , Huysmans Maaike , Vossen Emma , Boot Cécile , Anema Johannes
Published: March 2023

Objective

Workers with a lower socioeconomic position (SEP) often face problems on multiple life domains. This study evaluated an intervention to identify and solve problems on multiple life domains, called “Grip on Health.”

Methods

A mixed-methods process evaluation was performed among occupational health professionals (OHPs) and lower SEP workers with problems on multiple life domains.

Results

Thirteen OHPs delivered the intervention to 27 workers. For seven workers, the supervisor was involved, and for two, stakeholders from outside the workplace were involved. Agreements between OHPs with employers often affected implementation. OHPs were essential to help workers identify and solve problems. The intervention increased workers' health awareness and self-control, and led to small and practical solutions.

Conclusions

Grip on Health can support lower SEP workers with solving problems on multiple life domains. However, contextual factors make implementation difficult.
Adaptive and Maladaptive Cognitive-Emotional Strategies Associated With PTSD in First Responders
Authors: Tan Leona , Deady Mark , Bryant Richard A. , Harvey Samuel B.
Published: March 2023

Objective

To examine associations between cognitive-emotional strategies and posttraumatic stress disorder (PTSD) in first responders with high trauma exposure.

Method

Our study used baseline data from a cluster randomized controlled study of first responders across Colorado in the United States. Those with high exposure to critical incidents were selected into the current study. Participants completed validated measures of PTSD, emotional regulation and stress mindsets.

Results

A significant association was found for the emotion regulation strategy of expressive suppression and PTSD symptoms. No significant associations were found for other cognitive-emotional strategies. Logistic regression indicated that those with high use of expressive suppression were at significantly greater odds of probable PTSD compared to those with lower use (odds ratio, 4.89; 95% confidence interval, 1.37–17.41; P = 0.014).

Conclusions

Our findings suggest that first responders with high use of expressive suppression are at significantly higher risk of probable PTSD.
Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy
Authors: Ziogas Ioannis A. , Kakos Christos D. , Moris Dimitrios P. , Kaltenmeier Christof , Tsoulfas Georgios , Montenovo Martin I. , Alexopoulos Sophoclis P. , Geller David A. , Pomfret Elizabeth A.
Published: March 2023

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.
Additional Extracorporeal Membrane Oxygenation Pump Without an Oxygenator for Transseptal Left Atrial Decompression: A Case Report
Authors: Yang Jun Ho , Kim Jong Woo , Kang Dong Hoon , Moon Seong Ho , Kim Sung Hwan , Jung Jae Jun , Cha Ho Jeong , Byun Joung Hun
Published: March 2023

A 63-year-old man developed chest pain and dyspnea. Venoarterial-venous extracorporeal membrane oxygenation (ECMO) was applied to the patient due to failing heart after percutaneous coronary intervention. We used an additional ECMO pump without an oxygenator for transseptal left atrial (LA) decompression and performed a heart transplant. Transseptal LA decompression with venoarterial ECMO is not always effective for severe left ventricular dysfunction. Here, we report a case of the effective use of additional ECMO pump without an oxygenator for transseptal LA decompression through controlling the blood flow rate of the transseptal LA catheter.
Advances in inhaled antibiotics for management of respiratory tract infections
Authors: Riveiro Vanessa , Casal Ana , Abelleira Romina , Valdés Luis
Published: March 2023

Purpose of review

The incidence of bacterial respiratory tract infections is growing. In a context of increasing antibiotic resistance and lack of new classes of antibiotics, inhaled antibiotics emerge as a promising therapeutic strategy. Although they are generally used for cystic fibrosis, their use in other conditions is becoming more frequent, including no-cystic fibrosis bronchiectasis, pneumonia and mycobacterial infections.

Recent findings

Inhaled antibiotics exert beneficial microbiological effects in bronchiectasis and chronic bronchial infection. In nosocomial and ventilator-associated pneumonia, aerosolized antibiotics improve cure rates and bacterial eradication. In refractory Mycobacterium avium complex infections, amikacin liposome inhalation suspension is more effective in achieving long-lasting sputum conversion. In relation to biological inhaled antibiotics (antimicrobial peptides, interfering RNA and bacteriophages), currently in development, there is no still enough evidence that support their use in clinical practice.

The effective antimicrobiological activity of inhaled antibiotics, added to their potential to overcoming resistances to systemic antibiotics, make inhaled antibiotics a plausible alternative.
Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis
Authors: Ciapponi Agustín , Berrueta Mabel , Ballivian Jamile , Bardach Ariel , Mazzoni Agustina , Anderson Steven , Argento Fernando J. , Bok Karin , Comandé Daniel , Goucher Erin , Kampmann Beate , Parker Edward P. K. , Rodriguez-Cairoli Federico , Santa Maria Victoria , Stergachis Andy , Voss Gerald , Xiong Xu , Zaraa Sabra , Munoz Flor M. , Karron Ruth A. , Gottlieb Sami L. , Buekens Pierre M.
Published: March 2023

Introduction:

Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions.

Methods and analysis:

We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.
Retinal detachment secondary to bungee jump
Authors: Koirala Bipin , Sapkota Arjun
Published: March 2023

Introduction:

Bungee jumping is a recreational sport that involves head-first jumping from certain heights with an elastic cord attached to the person’s leg. It has the potential to develop ocular complications ranging from subconjunctival hemorrhage to retinal hemorrhage and even retinal detachment.

Case presentation:

Here, the authors report a case of a 28-year-old myopic male with Left-Eye retinal detachment secondary to a bungee jump.

Discussion:

In recent years, a few case reports have archived a variety of visual injuries caused by bungee jumping. But only few literatures have reported the event of retinal detachment related to bungee jumping. Patients with moderate to high myopic refractive error may have different vitreous and retinal changes, like vitreous degeneration, lattice degeneration, and peripheral retinal tears. The authors accept that these retinal findings are more related to the vitreoretinal traction mechanism leading to retinal detachment in bungee jumping.

Conclusion:

This case highlights that retinal detachment secondary to a bungee jump is a rare but serious ocular manifestation, and bungee jumping should be considered a risk factor for retinal detachment in predisposed patients
Examining Race-Based Discrimination, Depression, and Occupational Stress in Black Registered Nurses
Authors: Brandford Arica , Fernander Anita , Rayens Mary Kay , Mudd-Martin Gia
Published: March 2023

Nursing is a highly stressful and demanding profession that can negatively affect mental health, as shown by nurses' high rate of depression. Furthermore, Black nurses may experience additional stress due to race-based discrimination in the work environment. This research aimed to examine depression, experiences of race-based discrimination at work, and occupational stress among Black nurses. To better understand associations between these factors, we conducted multiple linear regression analyses to assess whether (1) past-year or lifetime experiences of race-based discrimination at work and occupational stress predicted depressive symptoms; and (2) controlling for depressive symptoms, past-year and lifetime experiences of race-based discrimination at work predicted occupational stress in a cohort of Black registered nurses. All analyses controlled for years of nursing experience, primary nursing practice position, work setting, and work shift. The results indicated that both past-year and lifetime experiences of race-based discrimination on the job were significant predictors of occupational stress. However, experiences of race-based discrimination at work and occupational stress were not significant predictors of depression. The results of the research highlighted the predictive effect of race-based discrimination on occupational stress in Black registered nurses. This evidence can inform the development of organizational and leadership strategies to improve the well-being of Black nurses in the workplace.
Promoting Safe Mobility Strategies for partnering with caregivers to maximize older adults' functional ability.
Authors: Olson Linda M. , Zonsius Mary C. , Rodriguez-Morales Grisel , Emery-Tiburcio Erin E.
Published: March 2023

This article is the fifth in a series, Supporting Family Caregivers in the 4Ms of an Age-Friendly Health System, published in collaboration with the AARP Public Policy Institute as part of the ongoing Supporting Family Caregivers: No Longer Home Alone series. The 4Ms of an Age-Friendly Health System (What Matters, Medication, Mentation, and Mobility) is an evidence-based framework for assessing and acting on critical issues in the care of older adults across settings and transitions of care. Engaging the health care team, including older adults and their family caregivers, with the 4Ms framework can help to ensure that every older adult gets the best care possible, is not harmed by health care, and is satisfied with the care they receive.

The articles in this series present considerations for implementing the 4Ms framework in the inpatient hospital setting and incorporating family caregivers in doing so. Resources for both nurses and family caregivers, including a series of accompanying videos developed by AARP and the Rush Center for Excellence in Aging and funded by The John A. Hartford Foundation, are also provided. Nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses. Cite this article as: Olson,L.M., et al. Promote Safe Mobility. Am J Nurs 2022; 122(7): 46-52.
The Interplay Between Walking Speed, Economy, and Stability After Stroke
Authors: Awad Louis N. , Knarr Brian A. , Kudzia Pawel , Buchanan Thomas S.
Published: March 2023

Background and Purpose:

Energy minimization is thought to underlie the naturally selected, preferred walking speed; however, people post-stroke walk slower than their most economical speed, presumably to optimize other objectives, such as stability. The purpose of this study was to examine the interplay between walking speed, economy, and stability.

Methods:

Seven individuals with chronic hemiparesis walked on a treadmill at 1 of 3 randomized speeds: slow, preferred, and fast. Concurrent measurements of speed-induced changes in walking economy (ie, the energy needed to move 1 kg of bodyweight 1 ml O2/kg/m) and stability were made. Stability was quantified as the regularity and divergence of the mediolateral motion of the pelvic center of mass (pCoM) during walking, as well as pCoM motion relative to the base of support.

Results:

Slower walking speeds were more stable (ie, pCoM motion was 10% ± 5% more regular and 26% ± 16% less divergent) but 12% ± 5% less economical. Conversely, faster walking speeds were 9% ± 8% more economical, but also less stable (ie, pCoM motion was 17% ± 5% more irregular). Individuals with slower walking speeds had an enhanced energetic benefit when walking faster (r
s = 0.96, P < 0.001). Individuals with greater neuromotor impairment had an enhanced stability benefit when walking slower (r
s = 0.86, P = 0.01).

Discussion and Conclusions:

People post-stroke appear to prefer walking speeds that are faster than their most stable speed but slower than their most economical speed. The preferred walking speed after stroke appears to balance stability and economy. To encourage faster and more economical walking, deficits in the stable control of the mediolateral motion of the pCoM may need to be addressed.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A416).
Interobserver Reproducibility in Assessing Eosinophilic Cells in Ovarian Serous Borderline Tumors to Predict BRAF Mutational Status
Authors: Chui M. Herman , Murali Rajmohan , Soslow Robert A. , Matrai Cathleen , Xing Deyin , Vang Russell
Published: March 2023

Ovarian serous borderline tumors (SBTs) harboring the BRAF
V600E mutation are associated with decreased risk of progression to low-grade serous carcinoma, and often prominently feature tumor cells with abundant eosinophilic cytoplasm. Since eosinophilic cells (ECs) may be a marker of the underlying genetic driver, we proposed morphologic criteria and evaluated the interobserver reproducibility for assessing this histologic feature. Following the completion of an online training module, representative tumor slides from 40 SBTs (BRAF
V600E-mutated, n=18, BRAF-wildtype, n=22) were independently reviewed by 5 pathologists. For each case, reviewers provided a semiquantitative assessment of the extent of ECs (0: absent, 1: <10%, 2: 10%–50%, or 3: >50%, of tumor area). Interobserver reproducibility for estimating the extent of ECs was moderate (κ=0.41). Applying a cut-off score of ≥2, the median sensitivity and specificity for predicting BRAF
V600E mutation were 67% and 95%, respectively. With a cut-off score of ≥1, median sensitivity and specificity were 100% and 82%, respectively. Morphologic mimics of ECs, including tumor cells with tufting or hobnail change and detached cell clusters in micropapillary SBTs, were possible contributing factors for discordant interobserver interpretations. BRAF
V600E immunohistochemistry showed diffuse staining in BRAF-mutated tumors, including those with few ECs. In conclusion, the finding of extensive ECs in SBT is highly specific for BRAF
V600E mutation. However, in some BRAF-mutated SBTs, ECs may be focal and/or difficult to distinguish from other tumor cells with overlapping cytologic features. The morphologic finding of definitive ECs, even when scarce, should therefore prompt consideration for BRAF

V600E mutation testing.
The Impact of Telemedicine Parity Requirements on Telehealth Utilization in the United States During the COVID-19 Pandemic
Authors: Lee Hyunjung , Singh Gopal K.
Published: March 2023

Background:

Research has shown a dramatic increase in telehealth utilization during the COVID-19 pandemic and marked socioeconomic disparities in telehealth utilization. However, previous studies have shown discrepant findings on the association between the state's telehealth payment parity laws and telehealth utilization, and dearth of differential impact studies by subgroups.

Methods:

Using a nationally representative Household Pulse Survey from April 2021 to August 2022 and the logistic regression modeling, we estimated the impact of parity payment laws on overall, video, and phone telehealth utilization and related disparities by race and ethncity during the pandemic.

Results:

We found that adults in parity states had 23% higher odds of telehealth utilization (odds ratio [OR] = 1.23; 95% confidence interval [CI], 1.14-1.33) and 124% higher odds of video telehealth utilization (OR = 2.24; 95% CI, 1.95-2.57) than their counterparts in nonparity states. In parity states, non-Hispanic White adults had 24% higher odds of telehealth utilization (OR = 1.24; 95% CI: 1.14, 1.35) and non-Hispanic Black adults had 31% higher odds of telehealth utilization (OR = 1.31; 95% CI: 1.03, 1.65), compared with those in nonparity states. For Hispanics, non-Hispanic Asians, and non-Hispanic other races, there was not a statistically significant effect of parity act on overall telehealth utilization.

Conclusions:

Given inequalities in telehealth utilization, increased state policy efforts are needed to reduce access disparities during the ongoing pandemic and beyond.
Effectiveness of Pelvic Floor Muscle Training for Patients Following Low Anterior Resection
Authors: Kim Young Man , Oh Eui Geum
Published: March 2023

PURPOSE:

The purpose of this systematic review was to identify the effects of pelvic floor muscle training (PFMT) on bowel function and health-related quality of life among patients who have undergone low anterior resection.

METHODS:

A systematic review and meta-analysis of pooled findings was conducted according to PRISMA guidelines.

SEARCH STRATEGY:

A literature search was completed using PubMed, EMBASE, Cochrane, and CINAHL electronic databases; we searched studies published in English and Korean languages. Two reviewers independently selected relevant studies, evaluated their methodological quality, and extracted data. Meta-analysis was conducted of pooled findings.

FINDINGS:

Thirty-six of 453 articles retrieved were read in full and 12 articles were included in the systematic review. In addition, pooled findings from 5 studies were selected for meta-analysis. Analysis revealed that PFMT reduced bowel dysfunction (mean difference [MD] −2.39, 95% confidence interval [CI] −3.79 to −0.99) and improved several domains of health-related quality of life: lifestyle (MD 0.49, 95% CI 0.15 to 0.82), coping (MD 0.36, 95% CI 0.04 to 0.67), depression (MD 0.46, 95% CI 0.23 to 0.70), and embarrassment (MD 0.24, 95% CI 0.01 to 0.46).

IMPLICATIONS:

Findings suggested PFMT is effective for improving bowel function and enhancing multiple domains of health-related quality of life after low anterior resection. Further well-designed studies are required to confirm our conclusions and provide stronger evidence for the effects of this intervention.
Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression
Authors: Li Yifan , Dang Xinglun , Chen Rui , Wang Junyang , Li Shiwu , Mitchell Brittany L. , Yao Yong-Gang , Li Ming , Li Tao , Zhang Zhijun , Luo Xiong-Jian
Published: March 2023

Deciphering the genetic architecture of depression is pivotal for characterizing the associated pathophysiological processes and development of new therapeutics. Here we conducted a cross-ancestry genome-wide meta-analysis on depression (416,437 cases and 1,308,758 controls) and identified 287 risk loci, of which 140 are new. Variant-level fine-mapping prioritized potential causal variants and functional genomic analysis identified variants that regulate the binding of transcription factors. We validated that 80% of the identified functional variants are regulatory variants and expression quantitative trait loci (eQTL) analysis uncovered the potential target genes regulated by the prioritized risk variants. Gene-level analysis, including transcriptome-wide association study (TWAS), proteome-wide association study (PWAS), colocalization and Mendelian randomization-based analyses, prioritized potential causal genes and drug targets. Combining evidence from different analyses revealed likely causal genes, includingTMEM106B, CTNND1, EPHB2, AREL1, CSE1L, RAB27B, SATU1, TMEM258, DCC, etc. Pathway analysis showed significant enrichment of depression risk genes in synapse-related pathways. Finally, we showed thatTmem106bknockdown resulted in depression-like behaviors in mice, supporting involvement ofTmem106bin depression. Our study identified new risk loci, likely causal variants and genes for depression, providing important insights into the genetic architecture of depression and potential therapeutic targets.