bluuebunny/crossref_metadata_2025 huggingface dataset:
NT-Pro-BNP and echocardiography for the early assessment of cardiovascular dysfunction in neonates with sepsis
Authors: Yang Chunyan , Ma Jing , Guo Lei , Li Baoyun , Wang Lina , Li Meixue , Wang Ting , Xu Ping , Zhao Cuifen
Published: September 2022

To investigate the predictive manner of N-terminal fragment of brain natriuretic peptide (NT-Pro-BNP) and echocardiography in the early assessment of cardiovascular dysfunction (CVD) in neonates with sepsis, we recruited 108 neonates with sepsis in intensive care units and divided them into a sepsis with CVD (sepsis + CVD) group (n = 48) and a sepsis only group (n = 60). Neonates with other infections (n = 65) constituted the control group. Clinical, laboratory, and bedside echocardiography findings were evaluated. Compared to both the sepsis only and control groups, the sepsis + CVD group showed an earlier onset of symptoms [52.94 (0–185.6) h], higher NT-Pro-BNP levels (P = .02), a higher Tei index (0.52 + 0.03; P = .03), and lower ejection fraction (62.61% ± 12.31%, P < .05). Compared to the control group, the sepsis + CVD group exhibited hematogenous etiology (P < .05), lower albumin (ALB) levels (P = .04), lower white blood cell counts (P = .03), a higher high-sensitivity C-reactive protein/ALB ratio, and a larger right-ventricle-inner diameter (10.74 + 2.42 mm; P = .01). CVD in the septic neonates could be predicted by either NT-Pro-BNP levels (cut-off: 12,291.5 pg/L; sensitivity, 80%; specificity, 79%; area under the curve-receiver operating characteristic, 0.81) or Tei index (cut-off: 0.45; sensitivity, 74%; specificity, 77%; area under the curve-receiver operating characteristic, 0.78). NT-Pro-BNP levels and echocardiography can be used to determine early onset of CVD in neonatal sepsis, which facilitates timely pharmacological interventions and treatment.
Antiplatelet agents aspirin and dipyridamole, and the risk of different carcinoma in patients with type 2 diabetes mellitus: A Taiwan retrospective cohort study
Authors: Huang Hsing-Yi , Lu Tz-Wen , Liang Hsiu-Ling , Hsu Wei-Hao , Sung Ya-Wen , Lee Mei-Yueh
Published: September 2022

Studies have shown aspirin decreases the risk of some cancers. However, the evidence reported the association between aspirin and cancer risk in the diabetic population. In this study, we investigate whether aspirin and dipyridamole decrease the risk of cancer in patients with type 2 diabetes. A total of 5308 patients with type 2 diabetes were identified by the National Health Insurance from 1998 to 2000 and followed up until 2013. The demographic characteristics among nondipyridamole nor aspirin, aspirin, and dipyridamole users were analyzed by using the χ(2) test. Cox proportional hazard regression models were used to determine the independent effects of no aspirin nor dipyridamole, aspirin, and dipyridamole users on the risk of different cancer. After adjustment with multiple covariates, both low and high doses of aspirin and dipyridamole decrease liver cancer with risk ratios of 0.56 (95% CI, 0.37–0.83), 0.14 (95% CI, 0.05–0.39), 0.61 (95% CI, 0.38–0.99), and 0.28 (95% CI, 0.12–0.66), respectively. Both low and high doses of aspirin decrease any types of cancer with risk ratios of 0.79 (95% CI, 0.64–0.98) and 0.49 (95% CI, 0.34–0.70), respectively. Therefore, we conclude aspirin may decrease any types of cancer and liver cancer, and dipyridamole may decrease the risk of liver cancer in patients with type 2 diabetes.
Comparison of tumor-associated and nontumor-associated esophageal mucosa microbiota in patients with esophageal squamous cell carcinoma
Authors: Zhang Baihua , Xiao Qin , Chen Huahai , Zhou Tao , Yin Yeshi
Published: September 2022

Esophageal microbiota plays important roles in esophageal squamous cell carcinoma (ESCC). The aims of this study were to clarify the changes in the bacterial community during ESCC development and identify latent pathogenic bacteria which may contribute to esophageal carcinogenesis and progression. Fresh tumor and nontumor esophageal mucosal samples were collected from 31 men with ESCC. High-throughput 16s rRNA sequencing was performed, and the operational taxonomic unit data and bacterial classification annotation were obtained and analyzed. The Ace, Chao, Shannon, Simpson indexes, and operational taxonomic unit numbers were higher in nontumor tissues than in tumor tissues, although without statistical significance. There were 4 phyla and 28 genera found to show significant differences between tumor and nontumor samples. The general probiotic Lactobacillus was 1.98-fold higher in nontumor tissues, while the general pathogenic genera Fusobacterium was 4.35-fold higher in tumor tissues. For tumor tissue samples, the genera Treponema and Brevibacillus were significantly higher in N1 and N2 stages, respectively, and Acinetobacter was significantly higher in T3 stage. For nontumor tissues, the genus Fusicatenibacter was significantly higher in T2 stage, and Corynebacterium, Aggregatibacter, Saccharimonadaceae-TM7x, and Cupriavidus were significantly higher in T4 stage. Additionally, bacteria related to nitrotoluene degradation were enriched in nontumor tissues, while bacteria related to base excision repair were enriched in tumor tissues. The relative abundance of several phyla and genera are different between tumor and nontumor tissue samples. The altered bacterial microbiota is correlated with different tumor stages and some microbes may take part in the carcinogenesis and development of ESCC.
Causal relationship between insomnia and tuberculosis: A bi-directional Mendelian randomization analysis
Authors: Zhang Shaobin , Zhang Wei , Feng Yan , Wan Shiqian , Ge Jing , Qu Zhaohui , Li Xin
Published: September 2022

Previous observational studies appear to have established a bi-directional association between sleep disorders and tuberculosis. However, their conclusions are prone to be biased by confounding effects and reverse causation due to the nature of observational studies. Mendelian randomization (MR) approach provides unconfounded estimates of causal effects and overcomes the limitations of observational studies. We performed a bi-directional MR analysis to clarify whether there existed a causal effect of insomnia on tuberculosis, or tuberculosis on insomnia. In forward-direction MR, we chose genome-wide significant (P < .5 × 10–8) and independent (r
2 < 0.001) single-nucleotide polymorphisms (SNPs) as instrumental variants (IVs), then extracted effect estimates of these IVs in tuberculosis genome-wide association study (GWAS) dataset to explore causal effect of genetically proxied insomnia on tuberculosis using inverse variance-weighted (IVW), MR-Egger, and weighted median methods. Additionally, we examined robustness and pleiotropy of effect estimates by heterogeneity and sensitivity analysis. Similarly, we investigated causal effect of genetically proxied tuberculosis on insomnia in reverse-direction MR. We revealed no causal relationship between genetically proxied insomnia and tuberculosis using 15 SNPs in forward-direction MR (IVW OR 5.305 [0.100–281.341], P = .410) and reverse-direction MR analysis (ORs and P values were not applicable due to no eligible SNPs in GWAS), with insignificant heterogeneity (Q = 22.6, I
2 < 0.001, P = .066) and pleiotropy (intercept = 0.032, SE = 0.057, P = .592) in effect estimates. Our bi-directional MR analysis affirms no causal effect of insomnia on tuberculosis, or tuberculosis on insomnia.
Which factors are helpful for the early determination of treatment level in patients with interstitial lung disease in the intensive care unit to minimize the suffering in their end of life?: A retrospective study
Authors: Kim Sun-Hyung , Lee Dong-Hwa , Yang Bumhee , Cho Jun Yeun , Kang Hyeran , Choe Kang Hyeon , Lee Ki Man , Shin Yoon Mi
Published: September 2022

Interstitial lung disease (ILD) is widely known to be associated with high mortality and poor prognosis, especially in patients admitted to the intensive care unit (ICU). The objective of this study was to investigate clinical predictors for assisting relatively early decision of treatment level in the ICU. We retrospectively investigated patients with ILD who were admitted to the ICU between January 1, 2014, and September 30, 2019. A total of 64 patients were analyzed. We found the ICU and hospital mortality rates to be 67.2% and 69.8%, respectively. Nonsurvivors had a higher fraction of inspired oxygen (FiO2) on days 1 (79 ± 21 vs 60% ± 21%, P = .001) and 3 (61 ± 31 vs 46% ± 19%, P = .004). They showed lower partial pressure of oxygen/FiO2 (PF) ratio on days 1 (134 ± 80 vs 173 ± 102, P = .049) and 3 (147 ± 74 vs 235 ± 124, P = .003) than the survivor group. The lactic acid levels obtained on day 1 and PF ratio measured on day 3 were associated with mortality (odds ratio, 1.89; 95% confidence interval 1.03–3.47 and odds ratio, 0.99; 95% confidence interval 0.98–1.00, respectively). Among the 31 ICU survivors, 10 patients died in the general ward, 12 patients died after hospital discharge; only 9 patients survived after 1 year. We suggest that these clinical predictors could be used to determine the level of further treatment or withdrawal on day 3 of admission in patients with ILD admitted to the ICU to minimize the prolonged suffering in a relatively early period.
When modern diagnostics is challenged by a historical disease: A case report
Authors: Jankowska Marta , Mross Krystian , Pałczyński Marcin , Machowska-Sempruch Karolina , Bajer-Czajkowska Anna , Parczewski Miłosz , Masztalewicz Marta
Published: September 2022

Rationale:

Syphilis is a bacterial, systemic infectious disease caused by Treponema pallidum spirochetes, which spread rapidly through the body affecting various organs. The term neurosyphilis (NS) refers to a CNS infection that can occur at any stage of the disease. The lack of a gold standard for the diagnosis of NS greatly hinders diagnosis, which must be based mainly on clinical assessment.

Patient concerns:

A 58-year-old man reported dizziness and headache for a week and right-sided hearing impairment, with suspected transient cerebral ischemic attack. A month later he experience transient speech disturbance and suspected cerebral ischemic stroke.

Diagnosis:

MRI showed fresh ischemic lesions with a diameter up to 10 mm in the deep brain structures on the left side and foci of subacute ischemia also in the deep structures and the brain stem. Cerebrospinal fluid examination showed positive Pandy’s reaction, doubtful Noone-Apelt reaction, increased protein level and decreased glucose level. The reactive result of the USR test performed (VDRL) finally allowed the diagnosis of symptomatic CNS syphilis.

Interventions:

Empiric treatment for bacterial meningitis was administered. The patient was transferred to the Department of Infectious Diseases for further treatment.

Outcomes:

The diagnosis has been confirmed at the Department of Infectious Diseases after repeating CSF analysis including VDRL and FTA-ABS.

Lesson:

Symptoms of NS are nonspecific, hence the diagnostic process is not straightforward. Despite the availability of modern diagnostic techniques, establishing a final diagnosis was challenging, but the patient ultimately received appropriate treatment. It is important to remember that syphilis is not only a disease known from history lessons but is still present in modern times and its incidence is increasing.
Automated and manual microscopic analyses for leukocyte differential counts in exudative pleural effusions: Real-world disagreement and clinical application
Authors: Lee Jaehee , Kim Yu Kyung , Park Ji Eun , Lee Yong Hoon , Choi Sun Ha , Seo Hyewon , Yoo Seung Soo , Lee Shin Yup , Cha Seung-Ick , Park Jae Yong , Kim Chang Ho
Published: September 2022

Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and <30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.
Bioinformatics-based identification of key genes and pathways associated with colorectal cancer diagnosis, treatment, and prognosis
Authors: Wang Chaochao , Zhang Li
Published: September 2022

Colorectal cancer (CRC) is known to display a high risk of metastasis and recurrence. The main objective of our investigation was to shed more light on CRC pathogenesis by screening CRC datasets for the identification of key genes and signaling pathways, possibly leading to new approaches for the diagnosis and treatment of CRC. We downloaded the colorectal cancer datasets from the Gene Expression Omnibus (GEO) database site. We used GEO2R to screen for differentially expressed genes (DEGs) of which those with a fold change >1 were considered as up-regulated and those with a fold change <-1 were considered as down-regulated on the basis of a P < .05. “Gene ontology (GO)” and “Kyoto Encyclopedia of Genes and Genomes (KEGG)” data were analyzed by the “DAVID” software. The online search tool “STRING” was used to search for interacting genes or proteins and we used Cytoscape (v3.8.0) to generate a PPI network map and to identify key genes. Finally, survival analysis and stage mapping of key genes were performed using “GEPIA” with the aim of elucidating their potential impact on CRC. Our study revealed 120 intersecting genes of which 55 were up- and 65 were downregulated, respectively. GO analysis revealed that these genes were involved in cell proliferation, exosome secretion, G2/M transition, cytosol, protein binding, and protein kinase activity. KEGG pathway analysis showed that these genes were involved in cell cycle and mineral absorption. The Cytoscape PPI map showed 17 nodes and 262 edges, and 10 hub genes were identified by top 10 degrees. Survival analysis demonstrated that the AURKA, CCNB1, and CCNA2 genes were strongly associated with the survival rate of CRC patients. In addition, CCNB1, CCNA2, CDK1, CKS2, MAD2L1, and DLGAP5 could be correlated to pathological CRC staging. In this research, we identified key genes that may explain the molecular mechanism of occurrence and progression of CRC but may also contribute to an improvement in the clinical staging and prognosis of CRC patients.
Prospective comparative study between knee alignment-oriented static and dynamic balance exercise in patellofemoral pain syndrome patients with dynamic knee valgus
Authors: Lee Jin Hyuck , Shin Ki Hun , Han Seung-Beom , Sun Hwang Kyo , Lee Seo Jun , Jang Ki-Mo
Published: September 2022

Exercise therapy has been reported as an effective treatment method for patellofemoral pain syndrome (PFPS). However, there is a lack of studies regarding the effectiveness of balance exercise in the treatment of patients with PFPS. This study aimed to prospectively compare changes in proprioception, neuromuscular control, knee muscle strength, and patient-reported outcomes between patients with PFPS treated with knee alignment-oriented static balance exercise (SBE) and dynamic balance exercise (DBE). The participants were divided into 2 groups: 17 knee alignment-oriented SBE group and 19 knee alignment-oriented DBE group. Proprioception was assessed by dynamic postural stability using postural stabilometry. Neuromuscular control and knee muscle strength were measured for acceleration time and peak torque in quadriceps muscle using an isokinetic device. Patient-reported outcomes were evaluated using a visual analog scale for pain and the Kujala Anterior Knee Pain Scale. There was greater improvement in dynamic postural stability (0.9 ± 0.3 vs 1.2 ± 0.5; 95% confidence interval [CI]: 0, 0.6; Effect size: 0.72;P = .021) and quadriceps AT (40.5 ± 14.3 vs 54.1 ± 16.9; 95% CI: 2.9, 24.2; Effect size: 0.86;P = .014) in the DBE group compared to the SBE group. Knee alignment-oriented DBE can be more effective in improving dynamic postural stability and quadriceps muscle reaction time compared with the knee alignment-oriented SBE in PFPS patients with dynamic knee valgus.
Prevalence and risk factors of sleep disturbance in adults with underlying health conditions during the ongoing COVID-19 pandemic
Authors: Kim Minjee , Opsasnick Lauren , Batio Stephanie , Benavente Julia Y. , Zheng Pauline , Lovett Rebecca M. , Bailey Stacy C. , Kwasny Mary J. , Ladner Daniela P. , Chou Sherry H.Y. , Linder Jeffrey A. , Weintraub Sandra , Luo Yuan , Zee Phyllis C. , Wolf Michael S.
Published: September 2022

To determine the prevalence of sleep disturbance during the coronavirus disease 2019 (COVID-19) pandemic among US adults who are more vulnerable to complications because of age and co-morbid conditions, and to identify associated sociodemographic and psychosocial factors. Cross-sectional survey linked to 3 active clinical trials and 2 cohort studies, conducted between 11/30/2020 and 3/3/2021. Five academic internal medicine practices and 2 federally qualified health centers. A total of 715 adults ages 23 to 91 years living with one or more chronic conditions. A fifth (20%) of participants reported poor sleep. Black adults were twice as likely to report poor sleep compared to Whites. Self-reported poor physical function (51%), stress (42%), depression (28%), and anxiety (36%) were also common and all significantly associated with poor sleep. Age ≥70 years and having been vaccinated for COVID-19 were protective against poor sleep. Sex, education, income, alcohol use, and employment status were not significantly associated with sleep quality. In this diverse sample of adults with chronic conditions, by race, ethnicity, and socioeconomic status, disparities in sleep health amid the ongoing pandemic were apparent. Worse physical function and mental health were associated with poor sleep and should be considered targets for health system interventions to prevent the many subsequent consequences of disturbed sleep on health outcomes. Measurements: self-reported sleep quality, physical function, stress, depression, and anxiety.
Cobas HPV Genotyping of FNA Sample Supernatant and Frozen Section Scrapings of Suspected Head and Neck Cancer
Authors: Jones Kelly J. , Dougherty Rachel E. , Randolph Melissa , Sim Michael W. , Mesa Hector
Published: September 2022

The human papillomavirus (HPV) status of squamous cell carcinomas (SCCs) of the head and neck is relevant for therapy planning, staging, and follow-up. Immunohistochemistry (IHC) for p16 is a surrogate marker of HPV status in oropharyngeal SCC, but not at other head and neck sites. We tested if the cobas HPV test was feasible and superior to p16-IHC on fine-needle aspiration (FNA) supernatants and frozen section (FS) scrapings of suspected SCC. A 500 μL aliquots of postcentrifugation supernatant CytoRich Red media of FNA cellblock specimens and scrapings of FS suspended in SurePath media vials were tested with the cobas HPV test and compared with p16-IHC and/or HPV in situ hybridization (ISH) performed on cellblock and/or resections. Twenty-nine (n=29) FNAs were tested for a cobas HPV test, p16, and/or HPV-ISH. The mean collection to testing time was 6.3 days (range: 0 to 24 d). Cobas yielded valid results in all cases; p16-IHC could not be interpreted in 4 (13%) cellblocks; correlation was performed on subsequent resections. Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FNA samples was 0.9, perfect agreement, sensitivity 100%, specificity 92.3%, positive predictive value 94.1%, negative predictive value 100%. Thirty-four (n=34) scrapings from FS were tested for cobas, p16, and/or HPV-ISH. The mean collection to testing time was 10.4 days (range: 1 to 28 d). Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FS scrapings was 1, perfect agreement. Sensitivity, specificity, positive predictive value, and negative predictive value was 100%. Cobas genotype was HPV-16 in 87%, HPV-18 in 3%, and HPV-other in 10%. Cobas HPV test in FNA supernatant and FS scrapings outperformed or was equivalent to p16-IHC and provided genotyping information.
Neighborhood Deprivation, Hospital Quality, and Mortality After Cancer Surgery
Authors: Bonner Sidra N. , Ibrahim Andrew M. , Kunnath Nick , Dimick Justin B. , Nathan Hari
Published: September 2022

Objective:

To evaluate if receipt of complex cancer surgery at high-quality hospitals is associated with a reduction in disparities between individuals living in the most and least deprived neighborhoods.

Background:

The association between social risk factors and worse surgical outcomes for patients undergoing high-risk cancer operations is well documented. To what extent neighborhood socioeconomic deprivation as an isolated social risk factor known to be associated with worse outcomes can be mitigated by hospital quality is less known.

Methods:

Using 100% Medicare fee-for-service claims, we analyzed data on 212,962 Medicare beneficiaries more than age 65 undergoing liver resection, rectal resection, lung resection, esophagectomy, and pancreaticoduodenectomy for cancer between 2014 and 2018. Clinical risk-adjusted 30-day postoperative mortality rates were used to stratify hospitals into quintiles of quality. Beneficiaries were stratified into quintiles based on census tract Area Deprivation Index. The association of hospital quality and neighborhood deprivation with 30-day mortality was assessed using logistic regression.

Results:

There were 212,962 patients in the cohort including 109,419 (51.4%) men with a mean (SD) age of 73.8 (5.9) years old. At low-quality hospitals, patients living in the most deprived areas had significantly higher risk-adjusted mortality than those from the least deprived areas for all procedures; esophagectomy: 22.3% versus 20.7%; P<0.003, liver resection 19.3% versus 16.4%; P<0.001, pancreatic resection 15.9% versus 12.9%; P<0.001, lung resection 8.3% versus 7.8%; P<0.001, rectal resection 8.8% versus 8.1%; P<0.001. Surgery at a high-quality hospitals was associated with no significant differences in mortality between individuals living in the most compared with least deprived neighborhoods for esophagectomy, rectal resection, liver resection, and pancreatectomy. For example, the adjusted odds of mortality between individuals living in the most deprived compared with least deprived neighborhoods following esophagectomy at low-quality hospitals (odds ratio=1.22, 95% CI: 1.14–1.31, P<0.001) was higher than at high-quality hospitals (odds ratio=0.98, 95% CI: 0.94–1.02, P=0.03).

Conclusion and Relevance:

Receipt of complex cancer surgery at a high-quality hospital was associated with no significant differences in mortality between individuals living in the most deprived neighborhoods compared with least deprived. Initiatives to increase access referrals to high-quality hospitals for patients from high deprivation levels may improve outcomes and contribute to mitigating disparities.
Three-Dimensional Mapping of Sternum Fractures from High-Energy Trauma
Authors: LaRoque Michael C. , Obermeier Michael C. , Cole Peter A.
Published: September 2022

Background

Sternum fractures are relatively uncommon injuries which generally occur as a result of a high-energy mechanism, and are often associated with significant concomitant injuries. These injuries may result in decreased quality of life if not properly addressed, and yet are rarely operated on. The purpose of this project is to evaluate high energy sternum fracture patterns using a previously published three-dimensional (3D) computed tomography (CT) reconstruction process to produce fracture frequency maps.

Methods

Patients aged 18 years and older presenting to a level 1 trauma center with sternum fractures due to high-energy trauma between October 2013 and January 2022 were included. A 3D reconstruction and reduction was performed for each sternum using medical image processing software (Materialise NV, Leuven, Belgium). The reconstructions were subsequently overlaid onto a template sternum and normalized using bony landmarks. Fracture lines for each injured sternum were transferred onto the template, creating 3D frequency maps.

Results

A total of 120 patients met inclusion criteria. The study population had a uniform age distribution and was 57.5% male. The most common mechanism of injury was motor vehicle collision (64.2%). The breakdown of sternum fractures were isolated sternal body (55.8%), isolated manubrium (31.7%), and combined sternal body and manubrium fractures (12.5%). No xiphoid fractures were observed. Sternal body fractures were a near even mix of transverse (31.7%), oblique (32.9%), and comminuted (35.4%), while 75.5% of manubrium fractures were oblique. The most common associated injuries included rib fractures (80.8%) and traumatic brain injury (61.7%).

Conclusions

This study presents the fractures from sternum injuries in 3D, and provides insight into reproducible sternum injury patterns that have not previously been analyzed in this format. This fracture mapping technique presents numerous injury patterns simultaneously such that more frequent morphologies can be appreciated for different patient groups.

Level of Evidence

Level IV, Diagnostic Test
A Method for Identifying the Learning Curve for the Surgical Stabilization of Rib Fractures
Authors: Delman Aaron M. , Turner Kevin M. , Ammann Allison M. , Millar D A. , Goodman Michael D. , Janowak Christopher F.
Published: September 2022

Introduction

Surgical stabilization of rib fractures (SSRF) is an accepted efficacious treatment modality for patients with severe chest wall injuries. Despite increased adoption of SSRF, surgical learning curves are unknown. We hypothesized intraoperative duration could define individual SSRF learning curves.

Methods

Consecutive SSRF operations between January 2017 to December 2021 at a single institution were reviewed. Operative time, as measured from incision until skin closure, was evaluated by Cumulative Sum (CUSUM) methodology using a range of acceptable “missteps” to determine the learning curves. Misstep was defined by extrapolation of accumulated operative time data.

Results

83 patients underwent SSRF by 3 surgeons during this retrospective review. Average operative times ranged from 135 minutes for 2 plates to 247 minutes for 7 plates. Using polynomial regression of average operative times, 75 minutes for general procedural requirements plus 35 minutes per plate were derived as the anticipated operative times per procedure. Cumulative sum analyses using 5%, 10%, 15% and 20% incident rates for not meeting expected operative times, or “missteps” were used. An institutional learning curve between 15-55 SSRF operations was identified assuming a 90% performance rate. An individual learning curve of 15-20 operations assuming a 90% performance rate was observed. After this period operative times stabilized or decreased for surgeons A, B, and C.

Conclusion

The institutional and individual surgeon learning curves for SSRF appears to steadily improve after 15-20 operations using operative time as a surrogate for performance. The implementation of SSRF programs by trauma/acute care surgeons is feasible with an attainable learning curve.

Level of Evidence

IV
Redefining the Costal Margin: A Pilot Study
Authors: Laswi Mujahed , Lesperance Rich , Kaye Adam , Bauman Zachary , Hansen Adam , Achay Jennifer , Kubalak Steven , Eriksson Evert
Published: September 2022

Background

Classical teaching of rib anatomy contends that the false ribs (7-10th) fuse anteriorly to form the costal margin of the chest. Slipped rib syndrome consists of false rib subluxation into the thorax with symptomatic impingement of the intercostal nerve. We sought to determine the incidence of this anatomic finding through anatomical study of the costal margin.

Methods

Cadavers were evaluated for mobility and attachment of the 9th and 10th ribs. Experienced anatomists and chest wall surgeons conducted a standardized dissection and assessed rib tip mobility using predefined criteria. Videos of dissections were submitted to a single investigator who reviewed the findings.

Results

Costal margins of 40 cadavers (45% male) were evaluated bilaterally. The average age was 83+/-11 years. The 9th rib was found to be attached to the 8th rib 100% of the time by an interchondral cartilaginous attachment along the body of the 8th and 9th ribs. Internal subluxation was noted in 19%(15/80) and the tip of the rib was mobile in 86%(69/80) evaluations. The 10th rib was attached to the 9th rib in 18%(14/80). A “floating” 10th rib was noted in 59%(47/80) of specimens. Subluxation was noted in 33% (26/60). Half of the ribs that subluxed moved medially to the 9th rib and half moved externally. An upwardly hooked tip was noted in 10%(8/80). Ribs with a hooked tip subluxed in 63% (5/8) and all of these ribs (5/5) moved to the interior of the chest (p = 0.020).

Conclusion

The 9th rib is commonly attached to the 8th rib, but the 10th rib is often not attached to the 9th rib. Most commonly, the 10th rib is a “floating” rib. Internal subluxation of the 10th rib as well as the presence of a hooked tip may predispose individuals to the development of “Slipped Rib Syndrome”.

Level of Evidence

Level II Diagnostic Test
PASC in Solid Organ Transplant Recipients With Self-reported SARS-CoV-2 Infection
Authors: Alasfar Sami , Chiang Teresa Po-Yu , Snyder Andrew J. , Ou Michael T. , Boyarsky Brian J. , Abedon Aura T. , Alejo Jennifer L. , Cook Sydney , Cochran Willa , Brigham Emily , Parker Ann M. , Garonzik-Wang Jacqueline , Massie Allan B. , Brennan Daniel C. , Vannorsdall Tracy , Segev Dorry L. , Avery Robin K.
Published: September 2022

Background.

Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization.

Methods.

A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration.

Results.

Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138–221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%).

Conclusions.

SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.
Diverse transcriptomic response of cellular system following low-dose exposure of mesoporous nanoparticles
Authors: Mittal Deepti , Ali Syed Azmal
Published: September 2022

Mesoporous nanoparticles (NPs) are an interesting drug delivery system that has generated considerable attention in the biomedical sector. Despite recent attempts to conduct safety assessments using traditional methods based on phenotypic data, our understanding of the underlying molecular processes produced by mesoporous NPs is still in its infancy. In the present study, RNA sequencing was used to assess the biological perturbations and the pathways induced in response to early exposure of two different mesoporous NPs; mesoporous silica NPs (MSN) and mesoporous carbon NPs (MCN) in human liver hepatocellular carcinoma cells. In order to better understand the risks associated with NPs, it is required to consider the initial low-dose exposure effects that mimic the real exposure scenario. No overt toxicity was detected in the MTT assay when performed at 6 hours at low concentrations (MCN 25 g/ml and MSN 15 g/ml) of NPs; thus, we have selected this dose for RNA sequencing analysis. Our transcriptomics analysis showed significant differences in the expression of many genes after exposure to both NPs. Surprisingly, both NPs frequently deregulated 52.9 percent of upregulated and 42 percent of downregulated genes. Gene ontology categories, in particular, revealed comparable perturbations of biological reactions in the cellular system. HepG2 cells reacted to mesoporous NPs by allowing alterations in genes involved in cytoskeleton reorganisation (ATAT1, DMTN, PTK2 and PFN2). Exposure to mesoporous NPs increased transcripts expressing ubiquitin ligase (RNF187, ARIH2, VHL, and RAB40C), transferase (FBXO3 and WDSUB1), conjugating (UBE2J2), and also proteasomal subunits (PSMD2, PSMD13) enzymes, indicating that protein turnover rates are altered in response to environmental damage. In addition, DNA damage and DNA damage checkpoint genes were upregulated, indicating that NPs induced stress in the cells. These finding showed low dosage acute exposure have comparable responses between mesoporous NPs. These results may add further knowledge in conceptualization of Safer-by-Design strategy of NPs in biomedical field.
Sympetrum sanguineum Newman, 1833 (Odonata, Anisoptera) - only one species with dimorphic females or two sibling species with identical males?
Authors: Felicia Babalean Anda
Published: September 2022

In this paper it is described a new Sympetrum species - Sympetrum bigeminus sp. nov. from Romania. The male of this new species is similar almost to identity with Sympetrum sanguineum from which differs only in the more conspicuous lateral thoracic sutures. The females are different from Sympetrum sanguineum by the vulvar scale, which is prominent (well visible in lateral view), incurved, with a deep concavity, and shortly bilobed, thus showing morphological characters of a different and distinct species.
Protein Kinase A Activity In The Leading Edge of Migrating Cells Is Dependent On The Activity of Focal Adhesion Kinase
Authors: Svec Kathryn V. , Kang Mingu , Howe Alan K.
Published: September 2022

Protein Kinase A (PKA) is a pleiotropic serine/threonine kinase whose localized and dynamic activity is required for cellular migration. Several cell types have shown robust PKA activity in the leading edge during migration. This activity is regulated by changes in actomyosin contractility, but the mechanism of the mechanochemical regulation of PKA remains unclear. Our ongoing investigation into this mechanism led us to discover a novel relationship between PKA and the non-receptor tyrosine kinase Focal Adhesion Kinase (FAK). Here, we find that while inhibition of actomyosin contractility leads to a relatively slow decrease in total cellular levels of phosphorylated FAK over tens of minutes, it decreases the focal adhesion-associated pool of both phospho-FAK and phospho-paxillin within two minutes, similar to the timing of the effect of inhibition of contractility on leading edge PKA activity. We then show that pharmacologic inhibition of FAK rapidly decreases leading edge PKA activity. Additionally, leading edge PKA activity is significantly reduced in FAK-null mouse embryonic fibroblasts and essentially eliminated by also silencing expression of the closely-related kinase Pyk2 in these cells. Importantly, leading edge PKA activity in FAK-null cells is rescued by re-expression of wild-type but not kinase-dead FAK. Taken together, these observations show that FAK activity is required for localized regulation of PKA during cell migration and, in so doing, establish a novel and unexpected connection between an adhesion-regulated tyrosine kinase and a serine/threonine kinase canonically downstream of G-protein coupled receptor and second-messenger signaling.
The Role of Frontal Eye Field in Saccadic Mixed-strategy Decision-making
Authors: Xie Siwei , Abunafeesa Abdullahi , Gu Yong , Yang Mingpo , Wang Xiaochun , Tu Jiahao , Thevarajah Dhushan , Dorris Michael Christopher
Published: September 2022

Game theory can predict the distribution of choices in aggregate during mixed-strategy games, yet the neural process mediating individual probabilistic choices remains poorly understood. Here, we examined the role of frontal eye field (FEF) in a decision-making task when macaques were trained to play a mixed-strategic game – Matching Pennies – against a computer opponent. Neuronal activities of FEF neurons predicted the animals’ upcoming saccadic choices and these activities became increasingly more selective as the choice deadline approached. Subthreshold electrical micro-stimulation applied in FEF also biased choices. Extended stimulation biased choices towards the preferred FEF vector whereas early termination of stimulation biased choices away from the preferred FEF vector. By contrast, micro-stimulation biased choices in the preferred direction during a non-strategic perceptual luminance discrimination task. We conclude that FEF is causally contributing to mixed-strategy decision-making process although the timing of FEF activation contributes to the decision process in a more non-linear manner during strategic compared to perceptual decision-making.
Medial accumbens shell spiny projection neurons encode relative reward preference
Authors: Pedersen Christian E. , Gowrishankar Raajaram , Piantadosi Sean C. , Castro Daniel C. , Gray Madelyn M. , Zhou Zhe C. , Kan Shane A. , Murphy Patrick J. , O’Neill Patrick R. , Bruchas Michael R.
Published: September 2022

Medial nucleus accumbens shell (mNAcSh) is a critical brain region for driving motivated behaviors. Despite this well-established role, the underlying reward processing of individual neurons, circuits and cell-types within mNAcSh remains largely unknown. Here, we leverage deep brain 2-photon calcium imaging through endoscopic lenses to record mNAcSh spiny projection neuron (SPN) ensemble responses to rewards of different concentrations and to reward-predictive cues across cue-reward learning. Reward responses were found to be heterogeneous and particularly differentiated based on reward concentration and cell type. A large subpopulation of reward-excited enkephalinergic SPNs were found to be specifically recruited during consumption of high concentration, unpreferred reward. A major enkephalinergic efferent projection from mNAcSh to ventral pallidum (VP) was also found to be recruited to high concentration but unpreferred reward and to causally drive low positive reward preference. Enkephalin and dynorphinergic SPNs in mNAcSh distinctly represent rewards of different preference and propagate distinct signals through efferent projections to drive consummatory behavior.
Vestigial-dependent recruitment contributes to robust patterning but is not required for wing-fate induction in Drosophila
Authors: Flores-Flores Marycruz , Muñoz-Nava Luis Manuel , Zartman Jeremiah , Nahmad Marcos
Published: September 2022

Cell recruitment is a process by which a differentiated cell induces neighboring cells to adopt its same cell fate. In Drosophila, cells expressing the wing selector gene, vestigial (vg), drive a feed-forward recruitment signal that propagates Vg expression suggesting that the Vg pattern is established as a wavefront throughout the wing pouch. However, the dynamics of Vg pattern formation does not meet this expectation. Here we show that an induction signal may drive Vg expression without Vg feedforward recruitment several cells away from the dorsal-ventral (DV) boundary. Particularly, when Vg expression is strongly inhibited either at the DV boundary or away from it, the activation of the vg Quadrant Enhancer still occurs at a distance, although the levels and precision of the pattern are compromised. Using live imaging of a dual-fluorescent reporter system, we show that contact-dependent cell recruitment does occur in wild-type conditions suggesting that a combination of a long-range induction signal and a signal-relay recruitment establishes Vg patterning in a robust manner. Overall, our findings reveal a previously unidentified role of cell recruitment as a robustness-conferring patterning mechanism.

Summary Statement

Robust formation of the Vg pattern is established by two mechanisms: a fast, long-range, but noisy induction signal; and a more precise signal relay, contact-dependent, cell recruitment process.
Target-template relationships in protein structure prediction and their effect on the accuracy of thermostability calculations
Authors: Lihan Muyun , Lupyan Dmitry , Oehme Daniel
Published: September 2022

Improving protein thermostability has been a labor- and time-consuming process in industrial applications of protein engineering. Advances in computational approaches have facilitated the development of more efficient strategies to allow the prioritization of stabilizing mutants. Among these is FEP+, a free energy perturbation implementation that uses a thoroughly tested physics-based method to achieve unparalleled accuracy in predicting changes in protein thermostability. To gauge the applicability of FEP+ to situations where crystal structures are unavailable, here we have applied the FEP+ approach to homology models of 12 different proteins covering 316 mutations. By comparing predictions obtained with homology models to those obtained using crystal structures, we have identified that local rather than global sequence conservation between target and template sequence is a determining factor in the accuracy of predictions. By excluding mutation sites with low local sequence identity (<40%) to a template structure, we have obtained predictions with comparable performance to crystal structures (R2 of 0.67 and 0.63 and an RMSE of 1.20 and 1.16 kcal/mol for crystal structure and homology model predictions, respectively) for identifying stabilizing mutations when incorporating residue scanning into a cascade screening strategy. Additionally, we identify and discuss inherent limitations in sequence alignments and homology modeling protocols that translate into the poor FEP+ performance of a few select examples. Overall, our retrospective study provides detailed guidelines for the application of the FEP+ approach using homology models for protein thermostability predictions, which will greatly extend this approach to studies that were previously limited by structure availability.
Influenza infection recruits distinct waves of regulatory T cells to the lung that limit lung resident IgA+ B cells
Authors: Sjaastad Louisa E. , Owen David L. , Joo Sookyong , Knutson Todd P. , O’Connor Christine H. , McCluskey Braedan , LaRue Rebecca S. , Langlois Ryan A. , Farrar Michael A.
Published: September 2022

The role of regulatory T cells (Tregs) in limiting responses to pathogens in tissues remains poorly described. We used scRNA-Seq and a newly generatedFoxp3-lineage reporter line (Foxp3-iDTRmice) to track Tregs in the lungs and peripheral blood following infection with influenza virus. Few Tregs of any type were found in the lung at steady-state. Following influenza infection Tregs expressing a strong interferon-stimulated gene signature (ISG-Tregs) appeared by day 3, peaked by day 7, and largely disappeared by day 21 post-infection. A second diverse wave of tissue-repair-like Tregs (TR-Tregs) appeared by day 10 and were maintained through day 21 post-infection. These two distinct Treg subsets had different gene expression patterns and distinct TCR repertoires. To establish the role of Tregs during influenza infection, we acutely ablated Tregs at day 6 post-infection; this resulted in a significant increase in IgA+ B cells in the lung. To determine whether distinct Tregs subsets could also be observed in response to respiratory viral infections in humans we analyzed scRNA-Seq datasets of patients with COVID-19. Peripheral blood from healthy human volunteers had multiple Treg subsets defined by unique gene expression patterns, but few ISG-Tregs. In contrast, two distinct Tregs subsets were expanded in COVID-19 patients - ISG-Tregs and IL32 expressing Tregs (16-fold and 2-fold increased, respectively). ISG-Tregs were present at significantly higher levels in patients with mild versus severe COVID-19, while IL32 expressing Tregs showed the opposite pattern. Thus, the Treg response to respiratory viruses in humans is also diverse and correlates with disease outcome.
Chaperones Hsc70 and Hsp70 Play Distinct Roles in Bocaparvovirus Minute Virus of Canines Infection
Authors: Guo Jianhui , Sun Jinhan , Yan Yan , Ji Kai , Hei Zhiping , Zeng Liang , Xu Huanzhou , Ren Xiang , Sun Yuning
Published: September 2022

Minute virus of canines (MVC) belongs to the genusBocaparvovirusand reproduces rapidly in its permissive cells Walter Reed/3873D (WRD). The crosstalk between MVC and WRD is poorly characterized in terms of molecular requirements and mechanisms. Here, we identified two novel cellular proteins Hsc70 and Hsp70 that interact with both NS1 and VP2 via mass spectrometry (MS), co-immunoprecipitation (Co-IP) and confocal immunofluorescence assays (IFA). Hsp70 was upregulated upon MVC infection. Respective silencing of Hsc70 and Hsp70 led to contrasting results at nearly every stage of MVC life cycle, including virus entry, transcription, translation, replication and production. Strikingly, transfection with low and high dose of pFlag-Hsp70 contributed to opposing impacts on viral protein levels and virus production possibly through a ubiquitin-dependent manner, indicating that MVC is quite sensitive to the levels of Hsp70. Treatment with quercetin and VER155008, two Hsp70 family inhibitors, both significantly decreased viral replication and particle levels. Together, these results illustrated that both Hsc70 and Hsp70 are involved in MVC life cycle, and targeting to Hsp70 family may represent a novel anti-MVC mechanism.