bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of Neonatal Respiratory Distress Syndrome by Tracheal Instillation of Surfactant
Authors: O’Donnell Colm P.F.
Published: August 2024

Surfactant deficiency was the suspected etiology of respiratory distress syndrome since 1959; after decades of bench and animal research to approach a safe and effective means of replacing surfactant, this was one of the first trials to show the immediate effects of surfactant on lung damage in infants. Infants born before 30 weeks at a single site who were intubated shortly after birth were randomly assigned to receive surfactant extracted from calf lungs (39 infants) or a sham injection of air (33 infants). Blood gas analysis showed improved oxygenation in the first 72 hours among infants who received surfactant. The a/A ratio was on average 0.15 higher in the surfactant group over the first 72 hours of life (p <0.05 at all time points). Fewer infants treated with surfactant had pulmonary interstitial emphysema on chest radiographs (3 versus 13; p <0.005), and fewer died in the neonatal period (1 versus 6; p <0.05).
Early CPAP Versus Surfactant in Extremely Preterm Infants
Authors: Manley Brett J.
Published: August 2024

The benefit of intubation for prophylactic surfactant was questioned as respiratory techniques evolved. The SUPPORT trial randomized 1316 extremely preterm infants born 24 to 27 weeks’ gestation to either early CPAP or intubation in the delivery room. This was in a 2×2 factorial trial, where oxygen saturation was also tested. After adjustment, the rate of the primary outcome of death or BPD did not differ significantly (CPAP 47.8% versus intubation 51.0%; RR 0.95, 95% CI 0.85 to 1.05, p = 0.30). However, on secondary analysis more infants in the CPAP group were alive and free from the need for mechanical ventilation by day 7 (55.3% versus 48.8%; RR 1.14, 95% CI 1.03 to 1.25, p = 0.01) and infants in the CPAP group required fewer days of ventilation (adjusted mean 24.8 versus 27.7; mean difference –3.0, 95% CI –5.6 to –0.3, p = 0.03).
A Trial Comparing Noninvasive Ventilation Strategies in Preterm Infants
Authors: Manley Brett J.
Published: August 2024

There was evidence from small trials that nasal intermittent positive pressure ventilation (NIPPV) might be a superior mode of respiratory support to nasal continuous positive airway pressure (nCPAP) for preterm infants. The NIPPV Trial randomized 1009 extremely low birth weight (ELBW) infants born before 30 weeks’ gestation to NIPPV or nCPAP, either as early or post-extubation respiratory support. A heterogeneous population was enrolled, involving 34 centers worldwide. This large, pragmatic trial allowed the use of both synchronized and non-synchronized NIPPV. The trial found no difference in the composite primary outcome of death or bronchopulmonary dysplasia at 36 weeks’ postmenstrual age (NIPPV 38.4% versus nCPAP 36.7%; adjusted odds ratio 1.09, 95% confidence interval 0.83 to 1.43, p = 0.56). There were no differences in the individual components of the primary outcome, or in the frequencies of other secondary outcomes, including potential adverse effects of treatment.
Effectiveness of Family Integrated Care in Neonatal Intensive Care Units on Infant and Parent Outcomes
Authors: Myttaraki Evangelia , Gale Christopher
Published: August 2024

Effective integration of parents in their newborn’s care is critical. This study evaluated the effect of Family Integrated Care (FICare), a pragmatic approach to enable parents to become their newborn’s primary caregivers in the NICU. In this international, multicenter, cluster-randomized controlled trial, 13 centers (895 infants) randomized to FICare were compared to 12 centers (891 infants) randomized to standard parental neonatal care. The primary outcome of infant weight gain at day 21 was greater in the FICare group (Z –0.071 [SD 0.42] versus –0.155 [0.42]; p <0.0002). Secondary outcomes of parental stress and anxiety were lower; and at discharge, high-frequency breastfeeding (≥6 times/day) was higher in the FICare group. No significant differences were found in other secondary outcomes between groups.
Interview Etiquette
Authors: Forstein David A. , Wardle Mark
Published: August 2024

Interviewing for a job in the medical profession is similar to looking for a job in any professional field. The employer, whether a private practice, hospital–physician group, or academic setting, will assume the applicant is capable of providing competent care based on postgraduate training and history of practice. Thus, employers typically assess professionalism, interpersonal and communication skills, fit with their organizational culture, and enthusiasm for the position. The applicant, in return, will also be assessing fit, growth potential, and organizational characteristics. This chapter provides information on interview structures, questions, and responses that will help the interview process be successful for both parties as well as assist in bringing out the desired information necessary to make decisions.
Reducing the Environmental Impact of Your Practice
Authors: Waberski Andrew T. , Pestieau Sophie R.
Published: August 2024

The concepts of climate change, ozone layer depletion, and the need for sustainability in equipment production are not novel, but what does this mean in the daily practice of anesthesiologists? Many healthcare professions are equipment-intensive and waste producing. At the forefront, operating rooms generate 20–30% of total hospital waste. To mitigate their environmental impact, healthcare systems and providers must implement change in practice by understanding resource life cycles, reducing equipment waste, and limiting release of greenhouse gases. As perioperative physician leaders, anesthesiologists are in a unique position to make environmentally sustainable choices for their patients, educate healthcare professionals, and establish green standards for perioperative care.
Lethal Injection
Authors: Baskerville Mark J.
Published: August 2024

For centuries, the medical profession has struggled with its role in executions for those condemned to death. Competing interests have failed to align a unified opinion among medicine, law, and ethics. Opponents argue that providers are using their medical knowledge and skills to end life, rather than preserve it. Several professional organizations, including the American Medical Association, have statements prohibiting practitioner involvement in execution. Proponents argue that medical providers are uniquely positioned to ensure a humane execution and that the medical profession has a duty to fix a broken process as long as capital punishment is accepted by society. The Supreme Court of the United States has opined that lethal injection is constitutionally acceptable as long as performed competently, potentially implicating the mandatory involvement of medical providers. Ultimately, the solution to this dilemma will require a multidisciplinary approach or the abolition of the death penalty.
Physician Employment Agreements
Authors: Hennessey Ian P.
Published: August 2024

It is very important for physicians to understand the key provisions of their employment agreements to minimize future unanticipated outcomes. Physicians should consider ways in which the agreement could go wrong and still be comfortable enough to execute the agreement rather than simply assume or hope for the best. It is important that a physician consider hiring an attorney whose practice is focused on healthcare matters, including employment agreements, to review the contract and its implications. An attorney may be in a better position to advise the physician on what are considered common or “market” conditions and what may or may not be applicable under the law. An attorney can also help negotiate changes in the employment agreement prior to signing.
The Contribution of Mitochondrial Evolution and Dysfunction to Neurodegeneration
Authors: Wasner Kobi , Pereira Sandro L. , Grünewald Anne
Published: August 2024

Mitochondria carry their own circular DNA but heavily depend on the import of nucleus-encoded proteins. During human brain evolution, a rapid increase in size and neuronal complexity was accompanied by elevated energy requirements, possibly explaining why neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease as well as mental disorders like schizophrenia—for which mitochondrial dysfunction is a hallmark—are specific to humans. This chapter summarizes the current understanding of the multifaceted involvement of mitochondrial signaling in normal aging and in neurological conditions with a focus on PD. Specifically, it concentrates on possible phylogenetic components in mitochondrial quality control, calcium dyshomeostasis, bioenergetics, and DNA maintenance as well as mitochondria-mediated apoptosis and inflammation. Finally, it discusses the challenges of mitochondria-targeted therapy approaches that aim at preventing the demise of dopaminergic neurons in PD patients.
Intrinsic Templates for Neurodegenerations Featuring Disease-Specific Axonal or Dendritic Vulnerability
Authors: Uchihara Toshiki
Published: August 2024

Human brain enlargement is associated with an increase of dendritic spines as well as axonal elongation and branching. These evolutionarily driven adaptations are hotspots for initiation of neurodegeneration in Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). They predict selective vulnerability for various protein deposits and propagation routes and are coined here disease-specific “intrinsic templates.” For instance, a human nigrostriatal axon is highly branched to yield 1,000,000 axon terminals. In PD, this highly branched non-myelinated axon templates distal-dominant initiation of degeneration, with local deposition of alpha-synuclein (αS). In ALS, these neurons accumulate TAR DNA-binding protein of 43 kDa but not αS deposits. Tau deposits in AD, as both three-repeat (3R) and four-repeat (4R) isomers, are seen in dendritic spines. 4R tau deposits in the early degenerative stage are replaced by 3R tau deposits to form ghost tangles in the later stage. This shift remains unexplained.
Contrast of muscle magnetic resonance imaging and pathological findings of muscle tissue in patients with anti-aminoacyl transfer RNA synthetase antibodies
Authors: Takei Hiroshi , Kondo Yasushi , Takanashi Satoshi , Takeuchi Tsutomu , Matsubara Shiro , Kaneko Yuko
Published: August 2024

Objectives

To determine whether magnetic resonance imaging (MRI) findings reflect the pathological features of inflammatory myopathies.

Methods

Patients with idiopathic inflammatory myopathies (IIMs) diagnosed using the 2017 European League Against Rheumatism/American College of Rheumatology classification criteria in our university between 2005 and 2020 were retrospectively reviewed. IIMs were subclassified into the anti-aminoacyl transfer RNA synthetase syndrome [anti-synthetase syndrome (ASSD)], immune-mediated necrotizing myositis, dermatomyositis (DM), and others. Fat-suppressed T2-weighted MRI and muscle biopsy specimens were assessed in IIMs followed by the comparison among the four subgroups.

Results

MRI findings were available for 62 patients and histopathological findings were available for 27 patients. Perifascicular atrophy or necrosis in the muscle tissues from the patients with IIM was more frequently observed in patients with subcutaneous and fascial high signal intensity (HSI) on MRI than those without. Four-group comparison among ASSD, immune-mediated necrotizing myositis, DM, and others revealed that HSI in fasciae on MRI was more frequently observed in patients with ASSD and DM than in others. Perifascicular atrophy or necrosis in muscle tissues was more frequently observed in patients with ASSD than in others.

Conclusion

Patients with ASSD had distinct MRI features compared with anti-aminoacyl transfer RNA synthetase negative patients. The fascial HSI on MRI may reflect distinctive pathological features of muscles.
Context-adjusted proportion of singletons (CAPS): a novel metric for assessing negative selection in the human genome
Authors: Gudkov Mikhail , Thibaut Loïc , Giannoulatou Eleni
Published: August 2024

Interpretation of genetic variants remains challenging, partly due to the lack of well-established ways of determining the potential pathogenicity of genetic variation, especially for understudied classes of variants. Addressing this, population genetics methods offer a practical solution by evaluating variant effects through human population distributions. Negative selection influences the ratio of singleton variants and can serve as a proxy for deleteriousness, as exemplified by the Mutability-Adjusted Proportion of Singletons (MAPS) metric. However, MAPS is sensitive to the calibration of the singletons-by-mutability linear model, which results in biased estimates for certain variant classes. Building up on the methodology used in MAPS, we introduce the Context-Adjusted Proportion of Singletons (CAPS) metric for assessing negative selection in the human genome. CAPS produces corrected estimates with more accurate confidence intervals by eliminating the mutability layer in the model. Retaining the advantageous features of MAPS, CAPS emerges as a robust and reliable tool. We believe that CAPS has the potential to enhance the identification of new disease-variant associations in clinical and research settings, offering improved accuracy in assessing negative selection for diverse SNV classes.
NANO-LM: An updated scorecard for the clinical assessment of patients with leptomeningeal metastases
Authors: Le Rhun Emilie , Nayak Lakshmi , Lim-Fat Mary Jane , Rudà Roberta , Pentsova Elena , Forsyth Peter , O’Brien Barbara J , Preusser Matthias , Kumthekar Priya , Brandsma Dieta , Weller Michael
Published: August 2024

Background

There are no validated tools for the clinical neurological assessment of patients with leptomeningeal metastases (LM). However, clinical examination during the course of the disease guides medical management and is part of response assessment in clinical trials. Because neuroimaging may not always be obtained owing to rapid clinical deterioration, clinical neurological assessment of LM is essential, and standardization is important to minimize rater disagreement.

Methods

The Response Assessment in Neuro-oncology-LM group launched a 2-step process, aiming at improving and standardizing the clinical assessment of patients with LM. We report here on the first step the establishment of a consensus scorecard. The task force had 9 virtual meetings to define general recommendations on neurological assessment and selected domains of interest that should be tested.

Results

Fourteen domains of neurological symptoms and signs were selected: level of consciousness, cognition, nausea and vomiting, vision, eye movement, facial strength, hearing, swallowing, speech, limb strength, limb ataxia, walking, and bladder bowel functions. For each item, a clear instruction on how to perform the assessment is provided with scoring criteria between 0 and 2. The general clinical status of the patient and use of steroids, pain medications, and antiemetics should be documented. Neurological sequelae from previous brain metastases or cancer treatment should be rated at the baseline evaluation; it should be specified when symptoms or signs may be related to a condition other than LM.

Discussion

A revised Neurological Assessment in Neuro-Oncology-LM consensus scorecard for clinical assessment has been established. An international prospective validation study of the proposal is currently ongoing (NCT06417710).
The quantitative trait locus GWY10 controls rice grain width and yield
Authors: Abbas Waseem , Sun Qi , Cui Yana , Shalmani Abdullah , Xu Pengkun , Fan Yawei , Zhang Dejian , Wu Meng-en , Li Xingxing , Li Yibo
Published: August 2024

A rice grain width and yield quantitative trait locus increases grain yield in near-isogenic lines and gene-edited lines and improves grain appearance and milling quality.
Patterns of soil-transmitted helminth aggregation in the human host population after several years of intensive mass drug administration
Authors: Mayer Julia , Collyer Benjamin S , Maddren Rosie , Abtew Birhan , Liyew Ewnetu Firdawek , Chernet Melkie , Tollera Getachew , Tasew Geremew , Anderson Roy M
Published: August 2024

Background

Community-wide mass drug administration (cMDA) is known as an effective, albeit costly, control strategy for soil-transmitted helminth (STH) parasites. A better understanding of STH aggregation after many rounds of cMDA could help shape more cost-effective policies.

Methods

This analysis uses data from the Geshiyaro project, aiming to break STH transmission by cMDA and water, sanitation and hygiene interventions. Ascaris lumbricoides infection prevalence is derived from egg count data and parasite aggregation is obtained by fitting a negative binomial distribution to the frequency distribution of faecal egg counts.

Results

The relationship between parasite dispersion and infection prevalence is approximately linear. Parasite aggregation increases as infection prevalence decreases.

Conclusions

A minority of individuals carry most parasites as prevalence decreases in the community. These individuals could be selectively targeted for repeated treatment.
Enhancing the Graduate Medical Education Clinical Learning Environment Through Community of Practice Forums
Authors: Woodruff James N. , Vela Monica B. , Lee Wei Wei , McConville John F.
Published: August 2024

An optimal clinical learning environment (CLE) is associated with improved learning and patient care outcomes. Significant concerns exist about the state of the CLE in graduate medical education (GME). Research suggests that GME programming falls short in interpersonal aspects of training that promote trainee engagement and psychological safety. Furthermore, published educational interventions in the CLE lack adequate theoretical backing to inform a rational approach to interventions in the CLE that could address these important problems.

The authors apply the 2002 work of Etienne Wenger on communities of practice (COP) to address these GME CLE concerns. To distinguish this COP intervention from earlier theoretical work on COPs, the authors refer to this management concept as “COP forums.” COP forums favorably influence the GME CLE through effects that complement experiential learning in patient care. COP forums support trainee psychological safety, mentorship from near peers, and opportunities to innovate—effects that can serve as a counterbalance to the time pressures, hierarchy, and compliance culture often experienced in the clinical environment. Deliverables of COP forums, including practice innovation and trainee self-efficacy, can favorably impact organization-wide performance and engagement.

This article describes the historical position of COP forums in the evolution of COP theory and outlines the basic structure and function of COP forums. It contrasts COP forums to other COP-related concepts to explain their relevance to the GME CLE. Examples of innovative GME COP forums illustrate the structure and function of these interventions. Finally, the authors call for more research on the impact of COP forums on the GME CLE. To avoid confusion, such scholarship must account for the ongoing evolution of the larger COP framework and target specific dimensions of the theory most pertinent to the medical education research question at hand.
Genetic Variants can Predict the Outcome of Brace Treatment in Patients With Adolescent Idiopathic Scoliosis
Authors: Dai Zhicheng , Min Kaixing , Wu Zhichong , Xu Leilei , Feng Zhenhua , Qiu Yong , Zhu Zezhang
Published: August 2024

Study design:

A genetic case-control study.

Objectives:

To investigate the association between AIS progression-associated SNPs reported by GWAS studies and the effectiveness of brace treatment.

Summary of background data:

Bracing is the most effective conservative method to treat adolescent idiopathic scoliosis (AIS). Several factors have been reported to be associated with bracing failure in AIS patients. Genetic markers associated with AIS have potential prognostic value.

Methods:

A retrospective cohort of AIS patients undergoing brace treatment was enrolled in this study and divided into success and failure groups based on treatment outcome. Clinical characteristics of AIS patients were documented. Candidate SNPs were selected from previous GWAS studies of AIS, which were known to be associated with curve progression and validated across diverse populations. Genotype and allele frequencies between the success and failure groups were compared using chi-square analysis.

Results:

A total of 259 female AIS patients were included in this study, 30.5% of the well-braced patients had curve progression exceeding 5° and 69.5% of the patients undergo an improvement or progression of less than 5°. Allele C of rs10738445 (BNC2) could significantly add to the risk of bracing failure, with odds ratio of 1.59. No significant association with bracing outcomes was found for rs12946942 (SOX9/KCNJ2), rs1978060 (TBX1), rs1017861 (CHD7), and rs35333564 (MIR4300HG).

Conclusions:

SNP rs10738445 were significantly associated with brace treatment effectiveness. The other four SNPs were not significantly associated with the outcome of bracing. More SNPs and predictors should be included in future study to develop a more accurate predictive model for clinical application.
Single-cell RNA Sequencing Analysis Reveals Cancer-associated Fibroblast Signature for Prediction of Clinical Outcomes and Immunotherapy in Gastric Cancer
Authors: Li Xiaoxiao , Tang Bo , Yujie Ouyang , Xu Chuan , Yuan Shuanghu
Published: August 2024

Gastric cancer (GC) is a significant worldwide health concern and is a leading cause of cancer-related mortality. Immunotherapy has arisen as a promising strategy to stimulate the patient’s immune system in combating cancer cells. Nevertheless, the effectiveness of immunotherapy in individuals with gastric cancer (GC) is not yet optimal. Thus, it is crucial to discover biomarkers capable appof predicting the advantages of immunotherapy for tailored treatment. The tumor microenvironment (TME) and its constituents, including cancer-associated fibroblasts (CAFs), exert a substantial influence on immune responses and treatment outcomes. In this investigation, we utilized single-cell RNA sequencing to profile CAFs in GC and established a scoring method, referred to as the CAF score (CAFS), for the prediction of patient prognosis and response to immunotherapy. Through our analysis, we successfully identified distinct subgroups within CAFs based on CAF score (CAFS), namely CAFS-high and CAFS-low subgroups. Notably, we noted that individuals within the CAFS-high subgroup experienced a lessF favorable prognosis and displayed diminished responsiveness to immunotherapy in contrast to the CAFS low subgroup. Furthermore, we analyzed the mutation and immune characteristics of these subgroups, identifying differentially mutated genes and immune cell compositions. We established that CAFS could forecast treatment advantages in patients with gastric cancer, both for chemotherapy and immunotherapy. Its efficacy was additionally confirmed in contrast to other biomarkers, including Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotypic Score (IPS). These findings emphasize the clinical relevance and potential utility of CAFS in guiding personalized treatment strategies for gastric cancer.
Assessing the Role of and Building a Business Case for Technology in Healthcare
Authors: Neumann C. Lydon , Blouin Ann Scott , Byrne Eileen Marie
Published: August 2024

As the healthcare market continues to evolve, technology plays a growing role in an integrated delivery system’s ability to provide high-quality, cost-effective care. Healthcare leaders must be proactive and forward-thinking about their technology investments because the financial investment for technology innovation can be significant. Healthcare leaders must deliberately design the role of technology and develop a consistent method for evaluating, identifying, and prioritizing technology investments. The article describes technology’s role in a healthcare organization as a window to the organization, a driver of business strategy, and a high-performance enabler. The article also develops a process for building a business case to ensure that an organization’s technology investments are well-reasoned and will provide value. In addition, the article discusses the importance of combining people and process reengineering with new technology to exponentially increase the value of an organization. Healthcare leaders must understand the multiple roles of technology and consistently develop a business case when making technology investment decisions.
More Than Under-Eye Bags: Treatment of Formidable Festoons
Authors: Chu Rachel L. , Godbe Kerilyn , Sciulli Harrison D. , Krachmalnick Sara J. , Abdo Maryam , Sokol Jason A.
Published: August 2024

A 64-year-old male with no medical care over the last decade was transferred from his local emergency room to a level 1 trauma center following an unwitnessed fall. Upon ophthalmic evaluation, he was noted to have significant lethargy and bilateral large festoons with secondary ectropion. Laboratory workup revealed severe hypothyroidism, consistent with myxedema coma, and his lethargy improved with medical treatment. The festoons were surgically removed to address the ectropion, and the patient was satisfied with the results following a single procedure. This case report features the largest reported festoons to date in the literature and emphasizes the importance of balancing cosmesis with function during surgical excision and correction of ectropion.
Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder
Authors: Arshadi Mahdi , Elmaadawi Ahmed Z. , Nasr Suhayl , Jayathilake Karu , Rassnick Stefanie , Ford Lisa , Drevets Wayne C. , Meltzer Herbert Y.
Published: August 2024

Background

The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo.

Methods

We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures.

Results

Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups.

Conclusions

This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.
Efficacy and safety of antireflux surgery in gastroesophageal-related cough: a systematic review and meta-analysis
Authors: Liu Yuheng , Huang Junfeng , Zhong Shuxin , Zheng Ziwen , Xu Zhixing , Zhou Dongda , Xie Shuojia , Lin Zikai , Li Shiyue , Chen Ruchong
Published: August 2024

Background:

Gastroesophageal reflux disease (GERD) is a prevalent condition that manifests a spectrum of symptoms, including gastroesophageal-related cough (GERC). Antireflux procedures have been employed to alleviate these symptoms, yet their efficacy varies. This systematic review and meta-analysis aim to evaluate the improvement in gastroesophageal-related cough and other reflux symptoms following antireflux procedures.

Methods:

A systematic review was performed by searching PubMed, Embase, and Cochrane Library. All observational studies reporting the improvement of GERC and other reflux symptoms after the antireflux procedures. Data were extracted and pooled using a random effects model to assess the overall effect size and heterogeneity between studies. The authors found that antireflux surgery has some clear benefits for common reflux-related symptoms.

Results:

Fifty-nine eligible studies with 7431 patients with GERD were included in this study. The pooled cough remission rate was 80.0% (95% CI: 75.4–84.2) and the mean time of follow-up was 35.8 months. Antireflux surgery significantly improved overall reflux-related symptom scores (all P<0.001). The authors also assessed the rate of remission of other reflux symptoms. The pooled heartburn remission rate was 87.7% (95% CI: 82.3–92.2) and the pooled regurgitation remission rate was 91.2% (95% CI: 87.8–94.1).

Conclusion:

Antireflux procedures significantly improve gastroesophageal-related cough and other reflux symptoms. These findings support the use of antireflux procedures as a viable treatment option for patients with GERD symptoms. Further research is needed to identify predictors of success and to optimize patient selection for antireflux procedures.
Hearing Loss in the Unoperated Ear After High-Speed Drilling in Otologic and Skull Base Surgery
Authors: Perez Philip , Tsai Tsung-Heng , Hawks John , Barbone Heather Malyuk , Pinkl Joey , Thirumala Partha , Bao Jianxin
Published: August 2024

Objective

To evaluate if permanent hearing loss occurred in the unoperated ear of patients undergoing otologic and skull base surgery with high-speed otologic drilling.

Study Design

We retrospectively studied 250 patients (mean age 57.8 yr; 120 males, and 130 females) undergoing otologic or skull base surgery with high-speed drilling between 2013 and 2019.

Setting

The University of Pittsburgh Medical Center.

Patients

We evaluated preoperative and postoperative audiograms for patients undergoing surgery for cochlear implantation (95 patients, 38.0%), cholesteatoma or chronic ear disease (88 patients, 35.2%), repair of lateral skull base encephalocele (26 patients, 10.4%), resection of vestibular schwannoma or meningioma of the cerebellopontine angle (23 patients, 9.2%), lateral temporal bone resection (8 patients, 3.2%), microvascular decompression (7 patients, 2.8%), or other operations involving a high-speed otologic drill (3 patients, 1.2%).

Main Outcome Measures

Hearing threshold shift, measured as the difference between postoperative threshold and preoperative threshold for each frequency. The association of age, gender, tested frequency, and surgery type with hearing threshold shift was investigated with analysis of covariance.

Results

A total of 102 patients (40.8%) had a 10-dB or greater worsening of their hearing in at least one frequency on their postoperative audiogram in the contralateral, unoperated ear. One hundred six subjects (42.4%) had no change in hearing of 10 dB or greater at any frequency. Among patients with longitudinal postoperative audiograms, accelerated age-related hearing loss was observed in low frequencies.

Conclusions

A significant number of patients demonstrated poorer hearing thresholds in the contralateral, unoperated ear after otologic and skull base surgery.
Beyond the Bedside
Authors: Obisesan Olawunmi , Tymkew Heidi , Gilmore Radhika , Brougham Nicole , Dodd Emily
Published: August 2024

Background:

Emerging evidence suggests that virtual patient observation (VPO) may help promote patient safety.

Purpose:

The purpose of this study was to examine and describe the demographic and clinical characteristics of patients who incurred VPO.

Methods:

A retrospective analysis was conducted. Differences in total VPO hours between groups were examined, followed by a hierarchical regression to investigate the effect of predictor variables on VPO utilization variance.

Results:

A total of 286 patient charts were reviewed. Mean VPO hours were higher in patients with an intensive care unit admission history. Adjusted for gender and history of dementia/Alzheimer’s/memory impairment, the prediction of total VPO hours increased with the patient’s intensive care unit admission history and overall hospital length of stay.

Conclusions:

Examining the prevalence and variability in the pattern of VPO utilization by specific patient characteristics is essential for identifying what patients could best benefit from this technology.
The Effect of Oral Mucosal Disinfection with Povidone-Iodine in Oral and Maxillofacial Surgery
Authors: Hu Liwei , Ye Xin , Zeng Xin , Duan Xiaohong , Xiu Qinghua , Ding Zhangfan , Liu Fan
Published: August 2024

This study enrolled 60 patients aged 28 to 76 years who were oral malignancy undergoing radical surgery for more than 3 hours to assess the disinfection effect of povidone-iodine in oral and maxillofacial surgery which is a clean-contaminated wound. The authors collected and compared the sample from oral mucosa and counted the colony-forming units before disinfection, after disinfection for 10 minutes, 1, 2, 3, and 4 hours. The results showed that the oral bacterial colony-forming units significantly decreased after disinfecting with povidone-iodine and the effect existed for 2 hours and the colony-forming units of 3 hours after disinfection showed statistically significant increase. In oral and maxillofacial surgery, povidone-iodine can effectively disinfect the mouth and maintain a certain period of time. Therefore, to reduce the number of oral mucosa microorganisms, it is recommended to disinfect the oral cavity again after 3 hours.
Vidian Canal in Chiari Type I Malformation: A Computed Tomography Study
Authors: Kilinç Mustafa Cemil , Zaimoglu Murat , Eroglu Umit , Özpişkin Ömer Mert , Erdin Engin , Güngör Berkay , Beger Orhan
Published: August 2024

Objective:

To evaluate the position and dimension of the Vidian canal (VC) in Chiari type I malformation (CIM).

Materials and Methods:

Radiologic views of 49 CIM (mean age: 23.58±15.62 y, sex: 23 males/26 females) and 51 healthy subjects (mean age: 42.50±20.12 y, sex: 21 males/30 females) were included in this computed tomography study.

Results:

In comparison with controls, the VC angle and the distance of the round foramen to VC were greater in CIM, but VC length and the distances of the superior wall of the bony sphenoidal sinus, midsagittal plane, and vomerine crest to VC were smaller in CIM. Relative to the sphenoid bone, the position of VC in CIM was determined as type 1 (59.2%) >type 2 (28.6%) >type 3 (12.2%), whereas in controls as type 1 (54.9%) >type 3 (25.5%) >type 2 (19.6%). Relative to the medial pterygoid plate, the position of VC in CIM was determined as type A (63.3%) >type B (20.4%) >type C (16.3%), while in controls as type B (43.1%) >type A (40.2%) >type C (16.7%).

Conclusion:

VC size and position correlated with CIM. Compared with controls, CIM patients had more partially protruded VC into the bony sphenoidal sinus and more medially located VC according to the medial pterygoid plate.
Methylomonas rivi sp. nov., Methylomonas rosea sp. nov., Methylomonas aurea sp. nov. and Methylomonas subterranea sp. nov., type I methane-oxidizing bacteria isolated from a freshwater creek and the deep terrestrial subsurface
Authors: Abin Christopher A. , Garner Christopher T. , Sankaranarayanan Krithivasan , Sindelar Reid A. , Kotary Kyrah F. , Garner Rosa M. , Barclay Samantha C. , Cai Haiyuan , Lawson Paul A. , Krumholz Lee R.
Published: August 2024

Four methane-oxidizing bacteria, designated as strains WSC-6T, WSC-7T, SURF-1T, and SURF-2T, were isolated from Saddle Mountain Creek in southwestern Oklahoma, USA, and the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. The strains were Gram-negative, motile, short rods that possessed intracytoplasmic membranes characteristic of type I methanotrophs. All four strains were oxidase-negative and weakly catalase-positive. Colonies ranged from pale pink to orange in colour. Methane and methanol were the only compounds that could serve as carbon and energy sources for growth. Strains WSC-6T and WSC-7T grew optimally at lower temperatures (25 and 20 °C, respectively) compared to strains SURF-1T and SURF-2T (40 °C). Strains WSC-6T and SURF-2T were neutrophilic (optimal pH of 7.5 and 7.3, respectively), while strains WSC-7T and SURF-1T were slightly alkaliphilic, with an optimal pH of 8.8. The strains grew best in media amended with ≤0.5% NaCl. The major cellular fatty acids were C14 : 0, C16 : 1 ω8c, C16 : 1 ω7c, and C16 : 1 ω5c. The DNA G+C content ranged from 51.5 to 56.0 mol%. Phylogenetic analyses indicated that the strains belonged to the genus Methylomonas, with each exhibiting 98.6–99.6% 16S rRNA gene sequence similarity to closely related strains. Genome-wide estimates of relatedness (84.5–88.4% average nucleotide identity, 85.8–92.4% average amino acid identity and 27.4–35.0% digital DNA–DNA hybridization) fell below established thresholds for species delineation. Based on these combined results, we propose to classify these strains as representing novel species of the genus Methylomonas, for which the names Methylomonas rivi (type strain WSC-6T=ATCC TSD-251T=DSM 112293T), Methylomonas rosea (type strain WSC-7T=ATCC TSD-252T=DSM 112281T), Methylomonas aurea (type strain SURF-1T=ATCC TSD-253T=DSM 112282T), and Methylomonas subterranea (type strain SURF-2T=ATCC TSD-254T=DSM 112283T) are proposed.
Aspiration pneumonia after SARS-CoV-2 Omicron infection frequently induced physical functional decline in Japan
Authors: Miyashita Naoyuki , Nakamori Yasushi , Ogata Makoto , Fukuda Naoki , Yamura Akihisa , Ito Tomoki
Published: August 2024

Introduction. Nursing and healthcare-associated pneumonia (NHCAP) mainly occurs in older people whose physical functions have declined, and it is the most common type of pneumonia in Japan, a super-ageing society. In older people who meet NHCAP criteria, respiratory tract infections are often accompanied by aspiration pneumonia.

Gap statement. The SARS-CoV-2 Omicron variant frequently causes aspiration pneumonia and has induced a decline in physical function.

Aim. To clarify functional outcomes at 1 year after hospital discharge in SARS-CoV-2 Omicron-related NHCAP cases.

Methodology. We compared the functional outcomes between 259 patients with primary SARS-CoV-2 pneumonia and 223 patients with aspiration pneumonia.

Results. Functional decline rates for calculating the Barthel index at the time of hospital discharge were higher in the aspiration pneumonia group than the primary SARS-CoV-2 pneumonia group [114 patients (51.6%) vs 70 patients (27.0%), P<0.0001]. Of 114 patients with aspiration pneumonia who had a decline in physical function at the time of hospital discharge, 91 (79.8%) still showed functional decline 1 year later. In contrast, 9.3% of patients had functional decline at 1 year after hospital discharge in the primary SARS-CoV-2 pneumonia group, which was significantly lower than in the aspiration pneumonia group.

Conclusions. The Omicron variant showed decreased infectivity in the lungs and was less pathogenic compared with the Delta and former variants. However, physicians should recommend SARS-CoV-2 vaccination and non-pharmaceutical interventions, depending on the presence or absence of applicable criteria for NHCAP, even when the predominant strain is the Omicron variant.
Methicillin-resistant Staphylococcus aureus outbreak in a Dutch equine referral clinic
Authors: Kannekens-Jager Marleen M. , Duim Birgitta , der Graaf-van Bloois Linda van , Zomer Aldert L. , Broekhuizen-Stins Marian J. , Boswinkel Maarten , Wagenaar Jaap A. , Broens Els M.
Published: August 2024

In 2020 and 2022, nine cases of surgical site infections with a methicillin-resistant Staphylococcus aureus (MRSA) were diagnosed in horses in an equine referral clinic. Sixteen isolates (horses, n=9; environment, n=3; and staff members, n=4) were analysed retrospectively using Nanopore whole-genome sequencing to investigate the relatedness of two suspected MRSA outbreaks (2020 and 2022). The MRSA isolates belonged to ST398 and ST612. ST398 genomes from 2020 and 2022 formed three phylogenetic clusters. The first ST398 cluster from 2020 consisted of isolates from five horses and one staff member, and we suspected within clinic transmission. The second cluster of ST398 isolates from 2022 originated from two horses and two staff members but showed higher single nucleotide polymorphism (SNP) distances. One ST398 isolate from an individual staff member was not related to the other two clusters. The ST612 isolates were isolated in 2022 from two horses and three environmental samples and showed very low SNP distances (<7 SNPs), indicating the transmission of MRSA ST612 in this clinic in 2022. Molecular characterization revealed an abundant set of virulence genes and plasmids in the ST612 isolates in comparison to ST398 isolates. Phenotypic antimicrobial susceptibility showed that differences between the two sequence types were consistent with the genetic characteristics. MRSA ST612 has not been reported in Europe before, but it is a dominant clone in African hospitals and has been described in horses and people working with horses in Australia, indicating the importance of surveillance.
Discovery of Novel, Potent and Orally Bioavailable SMARCA2 PROTACs with Synergistic Anti-tumor Activity in Combination with KRAS G12C Inhibitors
Authors: Kotagiri Sasikumar , Wang Yawen , Han Yanyan , Liang Xiaobing , Blazanin Nicholas , Nguyen Phuong Kieu , Jiang Yongying , Lissanu Yonathan
Published: August 2024

Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex includingSMARCA4in non-small cell lung cancer with a frequency of up to 33% in advanced stage disease, making it the most frequently mutated complex in lung cancer. We and others have identifiedSMARCA2to be synthetic lethal toSMARCA4,indicating SMARCA2 is a high value therapeutic target. Here, we disclose the discovery and characterization of potent, selective and orally bioavailable Cereblon-based SMARCA2 PROTACs. Biochemically, YDR1 and YD54 are potent SMARCA2 degraders with an average DC50of 7.7nM and 3.5nM respectively inSMARCA4mutant lung cancer cells. Phenotypically, both YDR1 and YD54 selectively inhibited growth ofSMARCA4mutant cancer cells. Further, we showed anti-tumor growth inhibitory activity of YDR1 and YD54 inSMARCA4mutant xenograft models of lung cancer. Finally, we show that YDR1 and YD54 synergize with the KRAS G12C inhibitor sotorasib to inhibit growth ofSMARCA4andKRAS G12Cco-mutant lung cancer cells. These findings provide additional evidence for the utility of single agent or combination regimens containing SMARCA2 PROTACs as synthetic lethal therapeutics againstSMARCA4mutant cancers.
Playtime for Cephalopods: Understanding the Significance of Play Behavior in Octopus bimaculoides
Authors: Jarmoluk Katarina , Pelled Galit
Published: August 2024

Play is considered to be an essential part of development that supports learning, memory, and the development of flexible behavioral strategies. An increasing amount of non-mammalian species have been discovered to engage in play behavior, but there has been little research into play behavior in cephalopods specifically. Here we studied play behavior of wild-caught, laboratory-housed California Two-Spot Octopuses,Octopus bimaculoides. The behavior observed in these animals is consistent with established criteria of play behavior in animals. The evidence of play inO. bimaculoidesprovides further insight into the evolutionary development of play behavior as a whole, the characteristics of play in an under-studied species, and also has the potential to be used as a factor in determining the welfare state of octopuses to improve their management in captivity.
Cluster Buster: A Machine Learning Algorithm for Genotyping SNPs from Raw Data
Authors: Martin Jessica , Kuznetsov Nicole , Levine Kristin , Koretsky Mathew J. , Hong Samantha , Nalls Mike A. , Vitale Dan
Published: August 2024

Genotyping single nucleotide polymorphisms (SNPs) is fundamental to disease research, as researchers seek to establish links between genetic variation and disease. Although significant advances in genome technology have been made with the development of bead-based SNP genotyping and Genome Studio software, some SNPs still fail to be genotyped, resulting in “no-calls” that impede downstream analyses. To recover these genotypes, we introduce Cluster Buster, a genotyping neural network and visual inspection system designed to improve the quality of neurodegenerative disease (NDD) research. Concordance analysis with whole genome sequencing (WGS) and imputed genotypes validated the reliability of predicted genotypes, with dozens of high-performing SNPs acrossLRRK2, APOE, andGBAloci achieving at least 90% concordance per SNP location. Further analysis of concordance between Genome Studio genotypes and imputed and WGS genotypes revealed discrepancies between the genotyping technologies, highlighting the need for selective application of Cluster Buster on SNP locations based on concordance rates. Cluster Buster’s implementation significantly reduces manual labor for recovering no-call SNPs, refining genotype quality for the Global Parkinson’s Genetics Program (GP2). This system facilitates better imputation and GWAS outcomes, ultimately contributing to a deeper understanding of genetic factors in NDDs.
Single-molecule diffusivity quantification inXenopusegg extracts elucidates physicochemical properties of the cytoplasm
Authors: Choi Alexander A. , Zhou Coral Y. , Tabo Ayana , Heald Rebecca , Xu Ke
Published: August 2024

The living cell creates a unique internal molecular environment that is challenging to characterize. By combining single-molecule displacement/diffusivity mapping (SMdM) with physiologically active extracts prepared fromXenopus laeviseggs, we sought to elucidate molecular properties of the cytoplasm. Quantification of the diffusion coefficients of 15 diverse proteins in extract showed that, compared to in water, negatively charged proteins diffused ∼50% slower, while diffusion of positively charged proteins was reduced by ∼80-90%. Adding increasing concentrations of salt progressively alleviated the suppressed diffusion observed for positively charged proteins, signifying electrostatic interactions within a predominately negatively charged macromolecular environment. To investigate the contribution of RNA, an abundant, negatively charged component of cytoplasm, extracts were treated with ribonuclease, which resulted in low diffusivity domains indicative of aggregation, likely due to the liberation of positively charged RNA-binding proteins such as ribosomal proteins, since this effect could be mimicked by adding positively charged polypeptides. Interestingly, negatively charged proteins of different sizes showed similar diffusivity suppression in extract, which are typically prepared under conditions that inhibit actin polymerization. Restoring or enhancing actin polymerization progressively suppressed the diffusion of larger proteins, recapitulating behaviors observed in cells. Together, these results indicate that molecular interactions in the crowded cell are defined by an overwhelmingly negatively charged macromolecular environment containing cytoskeletal networks.

Significance Statement

The complex intracellular molecular environment is notably challenging to elucidate and recapitulate.Xenopusegg extracts provide a native yet manipulatable cytoplasm model. Through single-molecule microscopy, here we decipher the cytoplasmic environment and molecular interactions by examining the diffusion patterns of diverse proteins inXenopusegg extracts with strategic manipulations. These experiments reveal an overwhelmingly negatively charged macromolecular environment with crosslinked meshworks, offering new insight into the inner workings of the cell.