bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin-mediated neural targets in obesity hypoventilation syndrome
Authors: Amorim Mateus R , Aung O , Mokhlesi Babak , Polotsky Vsevolod Y 
Published: July 2022

Abstract
Obesity hypoventilation syndrome (OHS) is defined as daytime hypercapnia in obese individuals in the absence of other underlying causes. In the United States, OHS is present in 10%–20% of obese patients with obstructive sleep apnea and is linked to hypoventilation during sleep. OHS leads to high cardiorespiratory morbidity and mortality, and there is no effective pharmacotherapy. The depressed hypercapnic ventilatory response plays a key role in OHS. The pathogenesis of OHS has been linked to resistance to an adipocyte-produced hormone, leptin, a major regulator of metabolism and control of breathing. Mechanisms by which leptin modulates the control of breathing are potential targets for novel therapeutic strategies in OHS. Recent advances shed light on the molecular pathways related to the central chemoreceptor function in health and disease. Leptin signaling in the nucleus of the solitary tract, retrotrapezoid nucleus, hypoglossal nucleus, and dorsomedial hypothalamus, and anatomical projections from these nuclei to the respiratory control centers, may contribute to OHS. In this review, we describe current views on leptin-mediated mechanisms that regulate breathing and CO2 homeostasis with a focus on potential therapeutics for the treatment of OHS.
Severe asthma and personalized approach in the choice of biologic
Authors: Di Bona Danilo , Spataro Federico , Carlucci Palma , Paoletti Giovanni , Canonica Giorgio W. 
Published: July 2022

Purpose of review
Severe asthma requires intensive pharmacological treatment to achieve disease control. Oral corticosteroids are effective, but their use is burdened with important side effects. Biologics targeting the specific inflammatory pathways underpinning the disease have been shown to be effective but not all patients respond equally well. As we treat more patients than those who can respond, our inability to predict responders has important healthcare costs considering that biologics are expensive drugs. Thus, a more precise choice of the ‘right patients’ to be prescribed with the ‘right biologics’ would be desirable.

Recent findings
Machine learning techniques showed that it is possible to increase our ability to predict outcomes in patients treated with biologics. Recently, we identified by cluster analysis four different clusters within the T2 high phenotype with differential benralizumab response. Two of these clusters, characterized by higher levels of inflammatory markers, showed the highest response rate (80–90%).

Summary
Machine learning holds promise for asthma research enabling us to predict which patients will respond to which drug. These techniques can facilitate the diagnostic workflow and increase the chance of selecting the more appropriate treatment option for the individual patient, enhancing patient care and satisfaction.
Management of endothelial disease without keratoplasty
Authors: Hakim Farida E. , He P. Cody , Veldman Peter B. 
Published: July 2022

Purpose of review
Currently, the most widely used treatment for endothelial disease is endothelial replacement via endothelial keratoplasty. Increasingly selective techniques have allowed for increased safety and faster visual recovery. However, alternative treatment options that are lower in cost, require less surgical expertise, and rely less on tissue availability are needed. This review discusses established and emerging therapies for endothelial disease without keratoplasty.

Recent findings
Regenerative therapies that have been successful include Descemet stripping only and Descemet membrane transplants. Rho-kinase inhibitors promote cell proliferation, adhesion, and migration and appear to have a role in these treatments and possibly in the prevention of endothelial disease. Cell-based therapies and the development of an artificial endothelial implant have also demonstrated promising results.

Summary
There are numerous emerging treatments for endothelial disease that have proven successful. Advances in our understanding of disease pathogenesis on a cellular level will continue to expand possibilities for therapeutics.
Impact of vaccination on keratoplasty
Authors: Dugan Sarah P. , Mian Shahzad I. 
Published: July 2022

Purpose of review
Corneal graft rejection has been reported after coronavirus disease 2019 (COVID-19) vaccination. The purpose of this review is to evaluate the literature regarding corneal graft rejection after vaccination, including rejection rates and risk factors. We aim to create a framework to identify patients who are at higher risk for graft rejection and may warrant consideration of prophylactic interventions.

Recent findings
Graft rejection has been reported following administration of mRNA, viral vector, and inactivated whole-virion COVID-19 vaccines. Most cases had additional risk factors associated with rejection. Vaccination increases circulation of proinflammatory cytokines, CD4+ and CD8+ T-cell responses, and antispike neutralizing antibody, all of which may contribute to graft rejection. Two prospective studies have found no relationship between recent vaccination and rejection but 20% of cornea specialists report to have seen a vaccine-associated rejection and 22% recommend delaying vaccination in certain circumstances. Many specialists recommend prophylactic topical corticosteroids before and after vaccination to mitigate rejection risk but there is no evidence to support this practice on a wider scale.

Summary
Our framework identified 96.8% of penetrating keratoplasty patients with vaccine-associated rejection as higher risk. Further research is needed in order to develop evidence-based guidelines.
Therapy for contact lens-related ulcers
Authors: Jeang Lauren , Tuli Sonal S. 
Published: July 2022

Purpose of review
The current review covers the current literature and practice patterns of antimicrobial therapy for contact lens-related microbial keratitis (CLMK). Although the majority of corneal ulcers are bacterial, fungus, and acanthamoeba are substantial contributors in CLMK and are harder to treat due to the lack of commercially available topical medications and low efficacy of available topical therapy.

Recent findings
Topical antimicrobials remain the mainstay of therapy for corneal ulcers. Fluoroquinolones may be used as monotherapy for small, peripheral bacterial ulcers. Antibiotic resistance is a persistent problem. Fungal ulcers are less responsive to topical medications and adjunct oral or intrastromal antifungal medications may be helpful. Acanthamoeba keratitis continues to remain a therapeutic challenge but newer antifungal and antiparasitic agents may be helpful adjuncts. Other novel and innovative therapies are being studied currently and show promise.

Summary
Contact lens-associated microbial keratitis is a significant health issue that can cause vision loss. Treatment remains a challenge but many promising diagnostics and procedures are in the pipeline and offer hope.
Advances in eye banking and corneal tissue processing
Authors: Li Jennifer Y. 
Published: July 2022

Purpose of review
Eye bank processing of donor corneal tissue has helped to revolutionize and popularize newer corneal transplantation surgeries. In particular, Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) have benefited from eye banks preparing donor corneal tissue in advance of the surgery. As a result of these eye banking advances, surgeons have been able to rapidly adopt these new techniques.

Recent Findings
This article reviews the techniques that are now being utilized to prepare donor tissue for endothelial keratoplasty (EK) with a focus on Ultrathin-DSAEK, prestamped, prestained, preloaded DMEK tissue, and advancements to improve the safety of donor corneal tissue.

Summary
Collaborative efforts between surgeons and eye banks have been at the core of advances that have been made in EK over the past decade. Corneal surgery starts in the eye bank, and it is important for corneal surgeons to understand the process and appreciate the efforts that have been made to provide them with suitable and safe donor corneal tissue.
Translating guidelines into practice via implementation science: an update in lipidology
Authors: Jones Laney K. , Sturm Amy C. , Gionfriddo Michael R. 
Published: July 2022

Purpose of review
Guidelines provide recommendations for clinicians based on the best available evidence and informed by clinical expertise. These recommendations often fail to be utilized by clinicians hindering the translation of evidence into practice. The purpose of this review is to describe novel ways in which implementation science has been used to improve translation of guidelines into clinical practice in the field of lipidology.

Recent findings
We searched PubMed for articles related to guideline implementation in lipidology published in 2021 and 2022. Identified articles were categorized into three domains: first, poor uptake of guideline recommendations in practice; second, implementation science as a solution to improve care; and third, examples of how implementation science can be incorporated into guidelines.

Summary
The field of lipidology has identified that many guideline recommendations fail to be translated into practice and has started to utilize methods from implementation science to assess ways to shrink this gap. Future work should focus on deploying tools from implementation science to address current gaps in guideline development. Such as, developing a systematic approach to restructure guideline recommendations so they are implementable in practice and aid in clinicians’ ability to easily translate them into practice.
Deep Learning for Fully Automated Prediction of Overall Survival in Patients Undergoing Resection for Pancreatic Cancer
Authors: Yao Jiawen , Cao Kai , Hou Yang , Zhou Jian , Xia Yingda , Nogues Isabella , Song Qike , Jiang Hui , Ye Xianghua , Lu Jianping , Jin Gang , Lu Hong , Xie Chuanmiao , Zhang Rong , Xiao Jing , Liu Zaiyi , Gao Feng , Qi Yafei , Li Xuezhou , Zheng Yang , Lu Le , Shi Yu , Zhang Ling 
Published: July 2022

Objective:
To develop an imaging-derived biomarker for prediction of overall survival (OS) of pancreatic cancer by analyzing preoperative multiphase contrast-enhanced computed topography (CECT) using deep learning.

Background:
Exploiting prognostic biomarkers for guiding neoadjuvant and adjuvant treatment decisions may potentially improve outcomes in patients with resectable pancreatic cancer.

Methods:
This multicenter, retrospective study included 1516 patients with resected pancreatic ductal adenocarcinoma (PDAC) from 5 centers located in China. The discovery cohort (n=763), which included preoperative multiphase CECT scans and OS data from 2 centers, was used to construct a fully automated imaging-derived prognostic biomarker—DeepCT-PDAC—by training scalable deep segmentation and prognostic models (via self-learning) to comprehensively model the tumor-anatomy spatial relations and their appearance dynamics in multiphase CECT for OS prediction. The marker was independently tested using internal (n=574) and external validation cohorts (n=179, 3 centers) to evaluate its performance, robustness, and clinical usefulness.

Results:
Preoperatively, DeepCT-PDAC was the strongest predictor of OS in both internal and external validation cohorts [hazard ratio (HR) for high versus low risk 2.03, 95% confidence interval (CI): 1.50–2.75; HR: 2.47, CI: 1.35–4.53] in a multivariable analysis. Postoperatively, DeepCT-PDAC remained significant in both cohorts (HR: 2.49, CI: 1.89–3.28; HR: 2.15, CI: 1.14–4.05) after adjustment for potential confounders. For margin-negative patients, adjuvant chemoradiotherapy was associated with improved OS in the subgroup with DeepCT-PDAC low risk (HR: 0.35, CI: 0.19–0.64), but did not affect OS in the subgroup with high risk.

Conclusions:
Deep learning-based CT imaging-derived biomarker enabled the objective and unbiased OS prediction for patients with resectable PDAC. This marker is applicable across hospitals, imaging protocols, and treatments, and has the potential to tailor neoadjuvant and adjuvant treatments at the individual level.
Therapeutic Interventions and Outcomes in Civilian and Military Isolated Gunshot Wounds to the Head
Authors: Benjamin Elizabeth R. , Demetriades Demetrios , Owattanapanich Natthida , Shackelford Stacy A. , Roedel Erik , Polk Travis M. , Biswas Subarna , Rasmussen Todd 
Published: July 2022

Objective:
The purpose of this study was to compare therapeutic strategies and outcomes, following isolated gunshot wounds of the head, between military and civilian populations.

Background:
Recent military conflicts introduced new concepts in trauma care, including aggressive surgical intervention in severe head trauma.

Methods:
This was a cohort-matched study, using the civilian Trauma Quality Improvement Program (TQIP) database of the American College of Surgeons (ACS) and the Department of Defense Trauma Registry (DoDTR), during the period 2013 to 2016. Included in the study were patients with isolated gunshots to the head. Exclusion criteria were dead on arrival, civilians transferred from other hospitals, and patients with major extracranial associated injuries (body area Abbreviated Injury Scale >3). Patients in the military database were propensity score–matched 1:3 with patients in the civilian database.

Results:
A total of 136 patients in the DoDTR database were matched for age, sex, year of injury, and head Abbreviated Injury Scale with 408 patients from TQIP. Utilization of blood products was significantly higher in the military population (P<0.001). In the military group, patients were significantly more likely to have intracranial pressure monitoring (17% vs 6%, P<0.001) and more likely to undergo craniotomy or craniectomy (34% vs 13%, P<0.001) than in the civilian group. Mortality in the military population was significantly lower (27% vs 38%, P=0.013).

Conclusions:
Military patients are more likely to receive blood products, have intracranial pressure monitoring and undergo craniectomy or craniotomy than their civilian counterparts after isolated head gunshot wounds. Mortality is significantly lower in the military population.

Level of Evidence:
Level III—therapeutic.
Operative and Nonoperative Outcomes of Emergency General Surgery Conditions
Authors: Kaufman Elinore J. , Keele Luke J. , Wirtalla Christopher J. , Rosen Claire B. , Roberts Sanford E. , Mavroudis Catherine L. , Reilly Patrick M. , Holena Daniel N. , McHugh Matthew D. , Small Dylan , Kelz Rachel R. 
Published: July 2022

Objective:
To determine the effect of operative versus nonoperative management of emergency general surgery conditions on short-term and long-term outcomes.

Background:
Many emergency general surgery conditions can be managed either operatively or nonoperatively, but high-quality evidence to guide management decisions is scarce.

Methods:
We included 507,677 Medicare patients treated for an emergency general surgery condition between July 1, 2015, and June 30, 2018. Operative management was compared with nonoperative management using a preference-based instrumental variable analysis and near-far matching to minimize selection bias and unmeasured confounding. Outcomes were mortality, complications, and readmissions.

Results:
For hepatopancreaticobiliary conditions, operative management was associated with lower risk of mortality at 30 days [−2.6% (95% confidence interval: −4.0, −1.3)], 90 days [−4.7% (−6.50, −2.8)], and 180 days [−6.4% (−8.5, −4.2)]. Among 56,582 intestinal obstruction patients, operative management was associated with a higher risk of inpatient mortality [2.8% (0.7, 4.9)] but no significant difference thereafter. For upper gastrointestinal conditions, operative management was associated with a 9.7% higher risk of in-hospital mortality (6.4, 13.1), which increased over time. There was a 6.9% higher risk of inpatient mortality (3.6, 10.2) with operative management for colorectal conditions, which increased over time. For general abdominal conditions, operative management was associated with 12.2% increased risk of inpatient mortality (8.7, 15.8). This effect was attenuated at 30 days [8.5% (3.8, 13.2)] and nonsignificant thereafter.

Conclusions:
The effect of operative emergency general surgery management varied across conditions and over time. For colorectal and upper gastrointestinal conditions, outcomes are superior with nonoperative management, whereas surgery is favored for patients with hepatopancreaticobiliary conditions. For obstructions and general abdominal conditions, results were equivalent overall. These findings may support patients, clinicians, and families making these challenging decisions.
Cardiovascular disease risk in people with severe mental disorders: an update and call for action
Authors: Rødevand Linn , Tesli Martin , Andreassen Ole A. 
Published: July 2022

Purpose of review
Cardiovascular disease (CVD) is a major cause of premature death in people with severe mental disorders (SMDs). This review provides an update on the level of CVD mortality and morbidity, as well as the socioeconomic, psychosocial and genetic factors associated with the comorbidity, and offer directions for improved interventions to reduce CVD in SMDs.

Recent findings
The level of CVD mortality and morbidity has sustained high in people with SMDs during the past decades, but the causal mechanism must be further elucidated. Psychosocial and socioeconomic challenges are frequent in SMDs as well as in CVD. Further, recent studies have revealed genetic variants jointly associated with SMDs, CVD risk and social factors. These findings highlight the need for more targeted interventions, prediction tools and psychosocial approaches to comorbid CVD in SMDs.

Summary
The level of CVD comorbidity remains high in SMDs, indicating that most people with SMDs have not benefitted from recent medical advances. A complex interplay between genetic and social vulnerability to CVD, which differs across subgroups of patients, seems to be involved. Further research is required to meet the urgent need for earlier, more efficient intervention approaches and preventive strategies for comorbid CVD in SMD.
The autism-associated Neuroligin-3 R451C mutation alters mucus density and the spatial distribution of bacteria in the mouse gastrointestinal tract
Authors: Herath Madushani , Bornstein Joel C , Hill-Yardin Elisa L , Franks Ashley E 
Published: July 2022

ABSTRACTThe intestinal mucus layer protects the host from invading pathogens and is essential for maintaining a healthy mucosal microbial community. Alterations in the mucus layer and composition of mucus-residing microbiota in people diagnosed with Autism Spectrum Disorder (ASD; autism) may contribute to dysbiosis and gastrointestinal (GI) dysfunction. Although microbial dysbiosis based on sequencing data is frequently reported in autism, spatial profiling of microbes adjacent to the mucosa is needed to identify changes in bacterial subtypes in close contact with host tissues. Here, we analysed the spatial distribution of the MUC-2 protein using immunofluorescence as well as total bacteria, Bacteroidetes, Firmicutes phyla and Akkermansia muciniphila (A. muciniphila) using fluorescent in situ hybridization in mice expressing the autism-associated R451C mutation in the Neuroligin-3 (Nlgn3) gene. We show that the Nlgn3 R451C mutation increases mucus density adjacent to the distal ileal epithelium in mice. The relative density of total bacteria, Firmicutes and A. muciniphila was increased whereas the density of Bacteroidetes was decreased closer to the epithelium in Nlgn3R451C mice. In summary, this study suggests that increased mucus density could contribute to mucosal microbial dysbiosis in ASD.
Rodent perirhinal cortex, but not ventral hippocampus, inhibition induces approach bias under object-based approach-avoidance conflict
Authors: Dhawan Sandeep S. , Pinter Carl , Lee Andy C. H. , Ito Rutsuko 
Published: July 2022

AbstractNeural models of approach-avoidance (AA) conflict behavior and its dysfunction have focused traditionally on the hippocampus, with the assumption that this medial temporal lobe (MTL) structure plays a ubiquitous role in arbitrating AA conflict. We challenge this perspective by using three different AA behavioural tasks in conjunction with optogenetics, to demonstrate that a neighbouring region in rats, perirhinal cortex, is also critically involved but only when conflicting motivational values are associated with objects and not contextual information. The ventral hippocampus, in contrast, was found not to be essential for object-associated AA conflict, suggesting its preferential involvement in context-associated conflict. We propose that stimulus type can impact MTL involvement during AA conflict and that a more nuanced understanding of MTL contributions to impaired AA behaviour (e.g., anxiety) is required. These findings serve to expand upon the established functions of the perirhinal cortex while concurrently presenting innovative behavioural paradigms that permit the assessment of different facets of AA conflict behaviour.
Benchmarking freely available human leukocyte antigen typing algorithms across varying genes, coverages and typing resolutions
Authors: Thuesen Nikolas Hallberg , Klausen Michael Shantz , Gopalakrishnan Shyam , Trolle Thomas , Renaud Gabriel 
Published: July 2022

The human leukocyte antigen (HLA) system is a group of genes coding for proteins that are central to the adaptive immune system and identifying the specific HLA allele combination of a patient is relevant in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods.We investigated the performance of five next-generation-sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq. This evaluation was done for the five HLA loci, HLA-A, -B, -C, -DRB1 and -DQB1 using whole-exome sequencing (WES) samples from 829 individuals. The robustness of the tools to lower coverage was evaluated by subsampling and HLA typing 230 WES samples at coverages ranging from 1X to 100X. The typing accuracy was measured across four typing resolutions. Among these, we present two clinically-relevant typing resolutions, which specifically focus on the peptide binding region.On average, across the five HLA genes, HLA*LA was found to have the highest typing accuracy. For the individual genes, HLA-A, -B and -C, Optitype’s typing accuracy was highest and HLA*LA had the highest typing accuracy for HLA-DRB1 and -DQB1.The tools’ robustness to lower coverage data varied widely and further depended on the specific HLA locus. For all class I loci, Optitype had a typing accuracy above 95% (according to the modification of the amino acids in the functionally relevant portion of the protein) at 50X, but increasing the depth of coverage beyond even 100X could still improve the typing accuracy of HISAT-genotype, Kourami, and STC-seq across all five HLA genes as well as HLA*LA’s typing accuracy for HLA-DQB1. HLA typing is also used in studies of ancient DNA (aDNA), which often is based on lower quality sequencing data. Interestingly, we found that Optitype’s typing accuracy is not notably impaired by short read length or by DNA damage, which is typical of aDNA, as long as the depth of coverage is sufficiently high.